Understanding Pancreatic Cancer: Causes, Symptoms, and the Path to Survival

Introduction

Pancreatic cancer is primarily a disease that results from damage to the deoxy ribonucleic acid (DNA). Such damage is frequently alluded to as mutations. The latter can be inherited from a male or female parent, or could be acquired with age. Individuals inherit two copies of each gene from their parents, one from the mother and the other from the father. The majority of the individuals with an inherited cancer syndrome, inherit one normal and one mutant copy of a gene associated with cancer (Johns Hopkins University). 

With the advancement of age, some of the individuals with an inherited cancer syndrome, experience damage to the normal copy of the gene in a pancreatic cell. As a result, that cell will possess two damaged copies of the gene. This will cause that pancreatic cell to exhibit abnormal growth that culminates in cancer. Therefore, it is not necessary that every individual who inherits a mutant copy of a malignant gene will develop cancer (Johns Hopkins University). However, persons with an inherited cancer syndrome, who are born with just one good copy of the cancer associated gene, are at greater risk of developing cancer. 

Symptoms

The classic symptoms associated with pancreatic cancer include: first, painless jaundice, which is associated with obstruction of the bile duct. Second, significant and inexplicable weight loss. Third, significant and newly developed abdominal pain. Fourth, upper abdominal pain that radiates to the back. Such pain being new, persistent and significant, and which is relieved by leaning forward. Fifth, back pain. Sixth, newly developed diabetes that is unrelated to increase in weight. Seventh, abdominal discomfort that does not respond to medication and dyspepsia. Eighth, loss of appetite. Ninth, vomiting and nausea. Tenth, pain at the time of eating. Eleventh, fatty excrement that is frequently foul smelling and pale (Pancreatic Cancer Action). 

Progression

Apparently, pancreatic cancer develops in a sequential manner that commences as normal pancreatic ductal epithelium to infiltrative carcinoma. In the majority of the instances, patients have little or no symptoms till the tumor develops to a locally unresectable stage. The initial stage in the development of pancreatic cancer is termed carcinoma in situ. The next stage of the disease is termed minute pancreatic cancer, where the tumor size is less than a centimeter in size. There are no symptoms experienced by the patient, even during this stage, and around 50% of the patients develop pancreatic duct dilation (Bhutani, Koduru and Joshi 9). 9

The third stage is called small pancreatic cancer, where the tumor is less than two centimeters in size. With the exception of a tumor that is proximate to the bile duct and which causes early obstructive jaundice, the patient does not experience any symptoms at this stage. Several among these patients have extra pancreatic spread at this stage. Finally, the tumor develops into a large pancreatic cancer that is greater than two centimeters in size, which is symptomatic and visible upon imaging.  (Bhutani, Koduru and Joshi 9). At this stage, only a proportion of these tumors are resectable.

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Statistics

Pancreatic cancer is a significant medical issue that has not been addressed satisfactorily. It has been identified as the reason behind for 338,000 diagnoses of cancer and 330,000 deaths, across the world, as of the year 2012. Despite being a rare cancer, the mortality it causes is considerably disproportionate with regard to all cancer deaths. As such, the chances of a five-year survival for a patient with pancreatic cancer is less than 5%. A major factor that enhances this disproportion is the late detection of this ailment, with the majority of the cases being diagnosed at an advanced stage of the disease (Pancreatic cancer: cause for optimism? 845).

Long-term survival can be ensured in some cases, via surgery. However, with regard to relapse of this disease, no standard options that prove to be effective have been developed. Prior to 1996, advanced, relapsed and metastatic disease had been treated palliatively with surgery, chemoradiation, or chemotherapy. Subsequently, approval of gemcitabine in the treatment of locally advanced or metastatic pancreatic cancer served to increase the five-year overall survival rate. Unfortunately, in the intervening two decades, new advances in the treatment of this dread disease have not transpired. This has been in marked contrast to the treatment of metastatic melanoma and non-small-cell lung cancer, wherein several new agents have provided a measure of relief (Pancreatic cancer: cause for optimism? 845). It is important to realize that immunotherapy has failed to achieve tangible results in the war against pancreatic cancer. 

Family History and Pancreatic Cancer

Pancreatic cancer admits of inherited vulnerability, and this has been demonstrated by several case reports. In fact, an early report on the prevalence of pancreatic cancer in females over successive generations, who had developed this disease at a younger age, had illustrated the clustering of pancreatic cancer. The authors of that report had conjectured that inheritance had an influence upon pancreatic cancer. In the year 1985, Lynch et al. described five generations of a family, in which there had been an early age onset of pancreatic and right-sided colon cancers. The prevalence of pancreatic cancer in that family had been viewed as being puzzling. Moreover, this family was regarded as being representative of hereditary non-polyposis colon cancer (Olson and Kurtz 3). Furthermore, that report had described what had subsequently termed a specific genetic susceptibility towards cancer of the pancreas. 

At present, two categories of hereditary risk for pancreatic cancer have come into vogue. Thus, familial pancreatic cancer has been described as an inherited tendency grounded upon family clustering in families with various first and second degree relatives with ductal pancreatic adenocarcinoma in the absence of an identified genetic susceptibility syndrome. Moreover, a family history of pancreatic cancer has been noticed among 5%-10% of the individuals with this disease. this disease tends to be a comparatively common form of cancer. Thus, several members of a family could be found to have this disease by mere chance. In addition, there could be common environmental factors, including smoking or high body mass index (Olson and Kurtz 3). As such, when there are several family members with pancreatic cancer, the risk of non-affected family members falling prey to it increases. 

Risk Factors

Pancreatic cancer involves very few established risk factors, which tend to be associated with other forms of cancer. Some of these being: tobacco smoke, age, gender, ethnicity, diabetes, obesity, genetic susceptibility, family and personal cancer history, chronic pancreatitis, and several occupational exposures. In addition, gall bladder disease and physical inactivity have been associated with this disease; however, these have not been established, on account of inconsistent data and absence of research (Kwabi-Addo and Lindstrom 90). 

Survey

In this regard, a 25-minute survey, involving 70 questions, had been prepared by the Pancreatic Cancer Action Network. These questions could be self-administered online. On account of this study, insight had been obtained regarding the actual experience of patients and caregivers in acquiring familiarity with the treatment choices available for pancreatic cancer. Despite the increase in the number of treatment options for this disease, a significant proportion of the respondents to this survey had expressed the absence of discussion with their physicians regarding these options. The gravity of the situation can be gauged from the fact that 95% of the patients tend to adopt the recommendations made by their physician (Engebretson, Matrisian and Thompson 229). 

Around 40% of the respondents, who had stated that the patient had not received treatment, had declared that the reason for the absence of treatment had been the physician’s opinion that there was no suitable treatment available. In another study, it had been discerned that 27% of the patients with stage I to II of pancreatic cancer had not been provided with treatment, and that just 47% had been subjected to surgery (Engebretson, Matrisian and Thompson 229). These facts emphasize the necessity for continuous medical education regarding the newly emerging treatment methods associated with pancreatic cancer, as well as the indispensability of unambiguous, persistent and meaningful dialogue between patients and physicians. 

Possible Treatment Options

An important consideration, in the treatment of pancreas cancer is the following. With regard to a disease that is not associated with targetable kinase over-activity and which is replete with difficult to target tumor suppressor gene mutations, the best option is to isolate treatment modalities that take advantage of other features of the biology of pancreatic cancer (Philip 826). 

In addition, the use of DNA repair deficiencies, including breast cancer (BRCA) gene mutations, constitutes an evolving personalized treatment modality that employs drugs that are approved. Gradually, the possibility of targeting the characteristic dense stroma associated with pancreatic adenocarcinoma is becoming a reality. This stroma had been conventionally described as being an impediment to the effective delivery of anti-cancer medication. An important consideration during this process is to ensure that the biology of the stroma has been carefully assessed, so that stromal targeting does not deteriorate the cancer by discarding elements with a detrimental effect upon the tumor cells (Philip 826). 

Moreover, family registries constitute a redoubtable resource in cancer research, and the study of pancreatic cancer kindreds has illustrated the familial aggregation of various cancers, including pancreatic cancer; quantified the risk of pancreatic cancer in high risk families; identified the pancreatic cancer susceptibility genes; and commenced the initial screening trials for pancreatic cancer. Active collaboration, has been in place, across family registries, and a sizeable number of the North American family registries are participating in the Pancreatic Cancer Genetic Epidemiology Consortium (Klein 73). 

Furthermore, the synchronization of data across various sites has been enabled by the gathering of comprehensive family history data and data on the recognized pancreatic cancer risk factors. Furthermore, there is a necessity for the special consideration of the consent associated with the collection of family data, as this will ensure the consistency of any collaboration with the original informed consent. The contemporary technological advances, which have facilitated whole-genome and whole-exome sequencing and collaborative ongoing sequencing endeavors, will make it possible to identify several novel pancreatic cancer susceptibility genes  (Klein 73). Moreover, individualized treatment plans that target these gene defects, as well as the improved screening of high-risk individuals, makes it feasible to diminish the mortality associated with pancreatic cancer.

Conclusion

As such, pancreatic cancer is a deadly disease, despite the availability of advanced treatments for it. Since, the symptoms are revealed at a later stage, survivor rate is very poor among the affected patients. In addition, the absence of medical knowledge about this disease and its treatment makes many, vulnerable to this deadly disease. Nevertheless, novel medical technologies such as whole- genome and whole-exome sequencing have made it possible to identify the gene defects, at an earlier stage, and thereby reduce pancreatic mortality.