Metastasis in the pancreatic cancer final

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  • 1. Metastasis in the Pancreatic Cancer Zuleika Velázquez Ortiz University of Puerto Rico at CayeyAbstract Pancreatic cancer is a tumor growth found in the pancreas that has a mortality rate almost equalto its incidence. The mayor problem of this disease is the metastasis process in which the tumorcell spread to other tissues or organs. Thereby, the purpose of this paper is to review what isknown about the metastasis process in pancreatic cancer patients. The first stage of metastasis inpatients with pancreatic cancer is not completely known. This is the result of the poor efficiencyof diagnosing the condition early. At the very moment of detecting the illness, the majority ofpatients diagnosed with pancreatic cancer are found in the advanced stage when metastasis hasalready occurred. Due to poor evidence or lack of evidence of pancreatic cancer in its earlystages it becomes impossible to further study the causes of cancerous cell propagation near thepancreas. Despite this, various investigations have been conducted on genes mutations such asthe Kras and tumor suppressor p16. Also, the expression of the Green Fluorescence Protein hasbeen used to identify tumor cells in the body.Introduction do research every day to find the causes of the disease, and highlight some carcinogensPancreatic cancer is a type of cancer such as obesity, diabetes, age, smoking,originated in the pancreas usually in the chemicals, and family history. Inheritanceexocrine cells. These cells are in charge of is one of the factors most studied (Pancreaticcreating gastric juices for the human body. Cancer ... 2012).However, there is also cancer in theendocrine cells. These cells are responsible The biggest problem with this disease isof producing insulin and glucagon, early detection, because when symptomshormones that stabilize the levels of sugar in occur the cancer is very advanced andthe blood. Malignant tumors are either metastasis has already occurred. Therefore,classified as endocrine or exocrine tumors. the purpose of this review paper is to examine what is known about the metastasisCurrently, pancreatic cancer is the fourth process in pancreatic cancer patients.leading cause of death for both, men and Metastasis is the process by which cancerwomen, containing a total of 6% of all the cells spread to the nearby organs of thecancers in the world (Siegel 2012). It is a initial place. In this case that place would begreat problem that society is facing, near the pancreas. This is the reason thatbecause pancreatic cancer is a disease that pancreatic cancer has a mortality rate almosthas no known causes. Hundreds of scientists equal to its incidence, with an estimated
  • 2. death rate of 85% of those diagnosed in consider the existence of a single type of2012 (Siegel 2012). There are four general pancreatic cancer, but there are twostages of pancreatic cancer and its classifications. This is due to the place ofsubdivisions. These are 0, IA, IB, IIA, IIB, origin of the tumor in the pancreas. A tumorIII, IV (Dunphy 2008). is the accumulation of cancer cells. When it settles in any part of the pancreas the tumor is called endocrine or exocrine tumor.II. Pancreatic Cancer A. Endocrine TumorThe pancreas is a gland of approximately 12to 15 cm long, located transversely in the Endocrine tumors, also calledcavity of the stomach. This organ has two neuroendocrine tumors, are a groupmain functions called exocrine and of homologous neoplasms originatedendocrine. Exocrine cells carry out the from cell islets or endocrine. Thedevelopment of hormones and enzymes for islet cells are cells located in thethe digestive process. On the other hand, it pancreas, and are responsible forhas an endocrine role in the islets of producing different types ofLangerhans producing insulin in the beta hormones such as glucagon orcells while the alpha cells produce glucagon. insulin. Less than 5% of pancreaticThese two hormones are responsible for the tumors are endocrine tumorsglucose levels in the blood. (Pancreatic Cancer Action Network 2012). Endocrine tumors can be.Pancreatic cancer is a tumor formation due benign or malignant and tend toto uncontrolled growth of abnormal cells evolve slower than exocrine tumors.(cancerous cells) somewhere in the These tumors are classified aspancreas. The exact causes of pancreatic functional (produce hormones) orcancer have not yet been discovered, but the nonfunctional (no hormones).main factors are considered to be exposure Different types of endocrine tumorsto viruses, carcinogens, genetic change, and are Gastrinoma, Glucagonoma,family history. This disease is highly Insulinoma, Endocrine Neoplasia,destructive due to the existence of so few Somatostatinoma, and Secretingsymptoms. Some of these are stomach pain, Tumor Vasoactive Intestinal Peptidevomiting, fatigue, dyspepsia, weight loss, (Pancreatic Cancer ... 2012).nausea, and a yellowish skin tone. B. Exocrine TumorThe detection of pancreatic cancer is donethrough a variety of tests such as computed Exocrine tumors have the highesttomography scanner (CT) and Laparoscopy. incidence of pancreatic cancers.Currently this type of disease has no specific Approximately 95% of the cases oftreatment, but surgery and subsequent pancreatic cancer originate inchemotherapy can be use. Most people exocrine cells. The exocrine cell
  • 3. tumors are also called Right after these cells produce the loss of a adenocarcinoma because they protein that maintains its union, dispersion originate at the gland cells. Exocrine begins to new places for the establishment cells are another type of pancreatic of tumor cells. (Massagué 2009). The lungs cells. They make enzymes that and liver are the most common places with a degrade fats, proteins, and high number of incidences of metastasis carbohydrates found in the caused by tumor cells. (Nguyen 2009). After pancreatic juice. The pancreatic juice inhabiting these places, metastasis continues secreted by the pancreas is necessary to spread continuously until it causes death for digestion in the body. These to its host. kinds of tumors are treated according to their status in the body and can be When the patient is diagnosed at stage IV of malignant (cancerous), benign cysts the disease it forecasts a 1.8% probability of living for 5 years (Pancreatic (non-cancerous) and benign tumors Cancer…2012). Stage IV is the one where (cystadenomas) (Pancreatic Cancer cancer cells have occupied distant places ... 2012). However most of these are malignant. from the pancreas causing the onset of metastasis (Dunphy 2008).III. Metastasis Stages of the Pancreatic CancerMetastasis is the process by which cancer Stages T N Mcells (tumor) continue to separate and Classification Classification Classificationdisperse quickly in different ways, settling Carcinoma in No spread to Metastasis isin another organ or tissue to form growth 0 situ regional not distant Tis lymph node M0elsewhere. This process is extremely fatal N0because when it spreads it is the ultimate Tumor in thestage to death for the person with the pancreas with N0 M0 IA no longer thandisease. Yachida et al. (2010) indicated as 2cmfollows: “Metastasis, the dissemination and T1growth of neoplastic cells in an organ Tumor in the pancreas N0 M0distinct from that in which they originated, IB longer thanis the most common cause of death in cancer 2cmpatients. This is particularly true for T2 Tumorpancreatic cancers, where most patients are extendsdiagnosed with metastatic disease and few outside the IIA pancreas but N0 M0show a sustained response to chemotherapy not to majoror radiation therapy”. blood vessels or nerves.In order for metastasis to begin, tumor stem T3cells are needed. They are the ones that reset T1 Spread to IIB T2 regional M0the propagation of tumor cells in the T3 lymph nodepancreas and in other different locations. N1
  • 4. Tumor difficult detection before the beginning of extends metastasis (Tran 2011). The GPF reveals outside the III pancreas to N1 M0 locations of the cancer cells in different major blood areas of the pancreas in the mouse model. vessels or nerves. This allows new techniques, subsequent T4 detection, and greater efficiency to provide a Distant longer life for patients with cancer. IV Any T Any N Metastasis M1Fig. 1 Cited in Dunphy EP. 2008. ConclusionsPancreatic Cancer: A Review andUpdate. C.J. of Oncology Nursing. Pancreatic cancer is a disease that has a12(5):735-741. According to the mortality rate almost equal to its incidence,(AJCC) TNM staging system deeply affecting both women and men of different ages who are diagnosed with thisAt this stage of metastasis, which causes malignancy. Moreover, metastasis remainsabout 90% of deaths for pancreatic cancer one of the biggest challenges for researcherspatients, cancer cells are unstoppable and of this deadly disease. Due to the greatimmune to treatment. Some scientists state difficulty of its detection, for beingthat metastasis occurs because healthy cells somewhat asymptomatic, metastasis isfrom other places attract the tumor cells and found to be advanced at the time of itsprovide a good place for their establishment. localization, and this hinders any furtherFurthermore, mutations have also been study. It is therefore very important tofound in different gens such as the Kras and develop better research for its earlyp16 as metastasis modulators. The gen Kras detection in the body.has been classified as an important factor for Acknowledgementthe proliferation and metastasis of thepancreactic cancer cells (Rachagani 2011). This work was made with the help of NicoleOn the other hand, the tumor suppressor M. Colón who helped me understand thep16INK4a has an inactivation in the majority structure and formation of metastasis inof pancreatic cancer patients so that allows Pancreatic Cancer.the tumor cell to develop in the body (Attri2005). References A. Green Fluorescence Protein in a mouse model. American Cancer Society [Internet]. 2012. Atlanta (GA): American Cancer Society;Green Fluorescence Protein (GFP) [revised 2012 Oct 16; cited 2012 Nov 24]expression in a mouse model was used to Available in:identify the tumor spread into other areas http://www.cancer.org/cancer/pancreaticcaninside and outside the pancreas despite its
  • 5. cer/detailedguide/pancreatic-cancer-what-is- Tran HS, Kaushal S, Menen RS, Metildicancer CA, Lee C, Snyder CS, Talamini MA, Hoffman RM, Bouvet M. 2011.Attri J, Srinivasan R, Majumdar S, Submillimeter-Resolution FluorescenceRadotra BD, Wig J. 2005. Alterations of Laparoscopy of Pancreatic Cancer in atumor suppressor gene p16INK4a in Carcinomatosis Mouse Model Visualizespancreatic ductal carcinoma. BMC Metastases Not Seen with StandardGastroenterology. 5(22):1-10. Laparoscopy. J. of Laparoendoscopic & A.DOI:10.1186/1471-230X-5-22 Surgical Techniques. 21(6):485-489. DOI: 10.1089/lap.2011.0181Dunphy EP. 2008. Pancreatic Cancer: AReview and Update. C.J. of Oncology Yachida S, Jones S, Bozic I, Antal T, LearyNursing. 12(5):735-741. R, Fu B, Kamiyama M, Hruban RH,Massagué J. 2009. Evolución y metástasis Eshleman JR, Nowak MA et al. 2010.del cáncer. SEBBM. 20(160):22-25. Distant metastasis occurs late during the genetic evolution of pancreatic cancer.Nguyen DX, Bos PD, Massagué J. 2009. Nature. 467(7319):1114-1117.Metastasis: from dissemination to organ- DOI:10.1038/nature09515.specific colonization. Nature. 9(4)-274-284.DOI:10.1038/nrc2622.Pancreatic Cancer Action Network[Internet]. Manhattan Beach (CA):Pancreatic Cancer Action Network; [citated2012 Nov 28]. Available in:http://www.pancan.org/section_facing_pancreatic_cancer/learn_about_pan_cancer/types_of_pancreatic_cancer/endocrine.phpRachagani S, Senapati S, Chakraborty S,Ponnusamy MP, Kumar S, Smith LM, JainM, Batra SK. 2011. Activated KrasG12D isassociated with invasion and metastasis ofpancreatic cancer cells through inhibition ofE-cadherin. British J. of Cancer.104(6):1038-1048.DOI:10.1038/bjc.2011.31Siegel R, Naishadham D, Jemal A. 2012.Cancer Statistics, 2012. CA: A CancerJournal for Clinicians. 62(1):10-29. DOI:10.3322/caac.20138.