Pancreatic Cancer, Anatomy of Pancreas - Research Paper Example

? Pancreatic Cancer - Pancreatic Cancer Introduction: Malignant cancers are considered to be among most devastating medical conditions not only because of associated high mortality rate but the way it affects the quality of life of the victim. The limited availability of the management options also add to the misery of medical physicians trying to combat with this deadly disease along with the patients. Much research has been conducted to understand the exact mechanisms involved in the development of malignant cells. In the past two decades, research has concluded that cancer is a genetic disease (Reber 1998). Alteration in the DNA molecules can lead an abnormal and uncontrolled growth of any cell. Although, cancer can affect virtually any cells in a human body pancreatic cancer has been a topic of debate because of its relatively poor prognosis and a reputation of being a silent killer. Among all cancer deaths, pancreatic cancer is assumed to be the fourth most common cause. Therefore, it is very crucial to understand the different types of pancreatic cancers and their clinical presentation to identify their existence at early stages. Anatomy of Pancreas: A review of anatomical location and orientation of pancreas is crucial as to diagnose an abdominal mass to be pancreatic in origin. Pancreas is an elongated retroperitoneal organ located transversely across the posterior abdominal wall. It lies posterior to the stomach between spleen and the duodenum. Pancreas can be divided into four parts that includes head, neck, body and tail. Head is the widest part and is situated in the C shaped curve of the duodenum. Inferior vena cava and the renal vasculatures are important structures in close proximity to the head of pancreas. The neck of the pancreas is a relatively short part that lies anterior to the Superior mesenteric vessels. Behind this part two important veins, superior mesenteric veins and splenic vein joins to form Portal vein. Body of the pancreas is a tapered part located posterior to the omental bursa and in close proximity to the aorta at the level of L2 vertebra. The tail also known as cauda pancreatis is the terminal end of the body and is situated near the gastric surface of the spleen. Because of its close association to the spleen much of the blood supply of this region is shared by the two organs. Physiological Function: Pancreas serves two main purposes in our body. It acts as both an exocrine and endocrine gland. The exocrine part of the pancreas forms about 90% of the total mass. The exocrine secretions include the pancreatic juices that are required for the digestion of the food. These secretions include enzymes such as amylase, lipase and proteases that are secreted into the pancreatic duct that opens into the duodenum. From the histological aspect, these exocrine secretions are produced by cells arranged into acini, known as acinar cells. They are trapezoid in shape and contain granular cytoplasm with nuclei located near the base. The rest of the 10% of pancreatic tissue is formed by the endocrine part that consists of islets of Langerhans distributed throughout the organ. But most of these endocrine cells are clustered at the tail end of the pancreas. Alpha and Beta cells are the two main types of endocrine cells that produce Glucagon and Insulin respectively. Other types of endocrine cells are also evident on immunohistochemistry that secretes vasoactive intestinal polypeptide (VIP), Somatostatin and other hormones. Pancreatic Cancer Epidemiology: In United States, pancreatic cancer is the fourth most common cause of cancer related mortalities. Certain factors predispose its occurrence in the general population such as age and gender. The data collected over the years has shown trends that the incidence of pancreatic cancer increases with age and it affect male population more than the female population with a 3 to 1 ratio for those younger than 40 years of age. The divergence of ratio between the gender declines slightly as the age of individuals increase above 40 years. Demographic distribution and ethnic variation has also been important factors in the epidemiological distribution of pancreatic cancer across the globe. For example, the incidence rate of pancreatic cancer in Israel was calculated that showed this rate to be 10.4 per 100,000 among male population of Europe or American origin and 5.6 per 100,000 among males born in Israel (Hidalgo et al 2004). Etiology: A number of different factors can contribute in the development of pancreatic cancer that includes genetic aspects, dietary habits, chronic pancreatitis, exposure to petroleum derivatives, alcohol and tobacco abuse. The role played by inheritance in the acquiring pancreatic cancer is still a topic of research but some evidences are there that some percentages of the pancreatic tumors are result of genetic cause. Certain cancer syndromes include pancreatic cancers as well as certain disease conditions such as cystic fibrosis and hereditary chronic pancreatitis. Certain studies showed some correlations of certain dietary intakes being associated with the development of pancreatic cancer. Coffee is considered to be a dietary risk factor as those diagnosed with pancreatic cancer had a strong history of coffee ingestion. Role of other dietary intakes either in excess or its deficiencies has been proposed to play a part in pancreatic cancer but so solid evidences are available. Alcohol and tobacco are also crucial factors that put an individual on a high risk of developing pancreatic cancer. Tobacco smoke is a risk factor for development of any type of cancer due to property of containing many carcinogens that can actually catalyze the process of mutation. It has been observed that pancreatic cancer is more common among patients suffering from chronic pancreatitis but the exact mechanism of how it brings about carcinogenic changes is not very clear. (Hidalgo et al 2004). Pathophysiology: The availability of modern molecular biological techniques in the study of tumor pathogenesis has revolutionized the understanding of different genes and their properties of either tumor suppression or tumor promotion. Alterations in the genes and formation of Oncogenes or deletion of genes responsible for providing resistance to autonomous growth of the cell are the key events that are responsible for pancreatic cancer. An in depth analysis of these Oncogenes and Tumor suppressor genes are required for the complete and thorough understanding of pathophysiology of pancreatic cancer. Oncogenes are not originally cancer promoting genes but they are the result product of mutation in the proto-oncogenes involved in normal growth signaling pathways of the cell. Either multiple copies of these normal genes are formed or their expression is enhanced by infusion with other genes so that they are co-expressed with them. Mutation in the K-ras gene is responsible for most of the pancreatic carcinomas. The prevalence of this mutation in pancreatic tumor is very high about 71 to 100%, which is highest compared to any other type of tumor (Reber 1998). The basic function of K-ras is to provide the signal transduction pathway of the growth promoting effectors from the cell surface. But mutation in some of the codons transforms K-ras into an oncogene. The GTPase activity is required to deactivate its activity. These mutations hinder this deactivation that results in over activation of this transduction system promoting uncontrolled growth and replication of pancreatic cell. Because K-ras mutation is among essential events required at early stages of pancreatic cancer, it can be used as a marker for early detection. (Reber 1998). Apart from K-ras other oncogenes such as MYC gene andAKT2 are believed to play part in the development in pancreatic neoplasm but there is not genetic proof that can confirm their contribution. Tumor suppressor genes are the group of genes that provide defense against the uncontrolled cellular proliferation. Normally two copies tumor suppressor genes, one from each parent, are found in any individual. But due to certain mutations both these copies can get corrupted leaving the cell defenseless against cancerous agents. Most common and well recognized tumor suppressor genes include p53 and p16 genes. Inactivations of p53 along with excessive activation of K-ras are two important events that greatly contribute in the development of pancreatic carcinoma. As discussed above, tobacco smoke is an important risk factor for the development of pancreatic cancer due to its carcinogenous contents. In a normal individual expression of p53 gene can effectively control the changes induced by these carcinogens. But individuals with inactive p53 gene such control are not available making them vulnerable to these insults. This highlights a very crucial concept regarding the pathophysiology of pancreatic cancer. Not one risk factor alone can effectively contribute in the development of this cancer but many different genetic and environmental factors combines together to promote the uncontrolled malignant proliferation of pancreatic cells. Different types: Pancreatic cancers can be classified based on the involvement of cellular lineage. Histological cell types of pancreas responsible for a particular tumor determine the pathological and biological characteristics. Pancreas has dual function as an endocrine and exocrine gland. But most of the tumors arise from the exocrine part of pancreas and belongs to a group of cancers known as adenocarcinoma which account for 90% of the total pancreatic malignancies. The most common adenocarcinoma is the pancreatic duct adenocarcinoma. Other less common exocrine tumors include acinar cell carcinoma, sarcoma and lymphomas. Tumors arising from the endocrine part include islet of Langerhans and Beta cell tumors, also known as “insulinoma”. Presentation/Complications: Most of the pancreatic tumors are diagnosed at a very late stage when the dissemination has already occurred. This is because he tumor progress very silently with no early signs and symptoms evident in the patient (Walsh et al 2009). Pancreatic duct adenocarcinoma being the most common type mostly develops in the head of the pancreas. Therefore, most of the patients present with the signs and symptoms of biliary obstruction such as jaundice. Further progression may result in the obstruction of the part of duodenum surrounding the C shaped head of the pancreas. In that case patient may present with symptoms of GIT obstruction that include nausea vomiting and bloating. Abdominal mass and associated pain radiating to the back is sometime the only complaint of patients later diagnosed with pancreatic cancer. Migratory thrombophlebitis is also sometimes associated with underlying pancreatic tumor. This signifies how nonspecific are presenting symptoms and greatly contribute in the late stage diagnose and associated mortality rates. Diagnosis: Detailed physical examination and the clinical evaluation with high suspicion for pancreatic cancer are very crucial for its diagnosis. Weight loss, decrease appetite, abdominal mass, jaundice and newly developed diabetes can be the warning signs for pancreatic cancer. But because of the non specific signs and symptoms clinical evaluation alone cannot be sufficient. Ultrasonography and use of radiographic imaging is essential for definitive diagnosis and staging the extent of tumor progression. CT scan is one most useful test for the diagnosis of pancreatic tumor. With the use of special contrast media and dedicated pancreatic CT scan, radiologists can outline the spread of this tumor to the nearby structures which is crucial for the staging and adopting an adequate management technique. For example it can help the surgeons to conclude if the tumor resection is possible or if it has progressed beyond the scope of surgical management. (O'Reilly et al 2003). Other important diagnostic procedures include MRI, Somatostatin receptor scintigraphy (SRS), PET scan and Endoscopic Retrograde Cholangiopancreatography (ERCP). MRI is specifically helpful to detect metastasis to brain and spinal cord. SRS is a unique but helpful technique of diagnosing pancreatic tumors. It uses radioactively bounded Octreotide that can attach to the proteins present on the tumor cells. A camera capable of identifying the radioactive Octreotide is used to pin point the location of these attachments. ERCP is a technique used to be cognizant of the pancreatic and bile duct patency using a dye injected into these ducts. Any obstruction can be a caused by pancreatic tumor originating in the head of pancreas. Blood tests are sometimes helpful by providing information about blood levels of certain tumor markers such as CA-19-9. But these markers are not very specific and their accuracy is still in debate. In endocrine tumors, however, blood tests can be very informative as blood levels of different pancreatic hormones can be determined and correlated clinically to arrive at a conclusion. Treatment: For those tumors, diagnosed at the early stage and where tumor resection is possible, surgery is the preferred choice of treatment. This can be followed by radiation therapy to reduce the chances of a relapse. But unfortunately, very less percentage of pancreatic cancer patients present at such early stage. Most of them are diagnosed at a very late stage with dissemination to surrounding structures such as liver. In that case, surgical resection will not be a completely valid management option. For metastatic pancreatic cancers chemotherapy is the choice of treatment with agents such as Gemcitabine or a combination with Capecitabine used as drug of choice. (Sheikh et al 2010). Five different types standard treatment options are available that include surgery, radiation therapy, chemotherapy, chemoradiation therapy and targeted therapy. In surgery, further options are available such as Whipple procedure, total pancreatectomy or distal pancreatectomy. Surgeons may choose what suits best for a particular patient. But if resection does not benefit the patient than a palliative surgery can be performed whereby biliary obstruction can be reversed or gastric bypass can be done to relieve certain symptoms of tumor compression. In targeted therapy drugs that specifically target the cancer cells without damaging the normal cells of the body are used. Tyrosine Kinase Inhibitors (TKIs) such as Erlotinib, are used in targeted therapy to treat pancreatic tumors. Bibliography Hidalgo Pascual,M., Ferrero Herrero,E., Castillo Fe,M. J., Guadarrama Gonzalez,F. J., Pelaez Torres,P., & Botella Ballesteros,F. (2004). Epidemiology and diagnosis of the pancreatic cancer: Epidemiologia y diagnostico. (Revista Espanola de Enfermedades Digestivas.) Revista Espanola de Enfermedades Digestivas. O'Reilly, E. M., & Kelvin, J. F. (2003). 100 questions & answers about pancreatic cancer. Sudbury, Mass: Jones and Bartlett. Reber, H. A. (1998). Pancreatic cancer: Pathogenesis, diagnosis, and treatment. Totowa, New Jersey: Humana Press. Sheikh, Rizwan, Walsh, Naomi, Clynes, Martin, O'Connor, Robert, & McDermott, Ray. (2010). Challenges of drug resistance in the management of pancreatic cancer. (Sheikh, Rizwan and Walsh, Naomi and Clynes, Martin and O'Connor, Robert and McDermott, Ray (2010) Challenges of drug resistance in the management of pancreatic cancer. Expert Review of Anticancer Therapy, 10 (10). pp. 1647-1661. ISSN 1473-7140.) Expert Reviews. Walsh, Naomi, Clynes, Martin, Crown, John, & O'Donovan, Norma. (2009). Alterations in integrin expression modulates invasion of pancreatic cancer cells. (Walsh, Naomi and Clynes, Martin and Crown, John and O'Donovan, Norma (2009) Alterations in integrin expression modulates invasion of pancreatic cancer cells. Journal of Experimental & Clinical Cancer Research, 28 (140). ISSN 1756-9966.) BioMed Central. Read More