Pancreatic Cancer According To The Literature 

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CONTACT N.H. TO LEARN MORE ABOUT ALTERNATIVES TO THE CURRENT PRACTICE OF DIAGNOSING AND TREATING PANCREATIC CANCER.

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Pancreatic cancer, although with its relatively low incidence, is still regarded as the seventh leading cause of cancer-related deaths worldwide (Bray F, 2018). This intractable malignancy demonstrates a high mortality rate due to typically late onset of diagnosis and early metastasis to surrounding organs such as the liver, abdominal wall, lungs, and bones, etc. According to GLOBOCAN 2018 estimates, pancreatic cancer remains one of the most lethal malignant neoplasms, with around 432,242 new deaths recorded in 2018 alone. This was also proposed to be due to the delay in the manifestation of symptoms until an advanced stage of the disease. This 11th most common malignancy worldwide has a slight male predominance in comparison to females. The incidence in both sexes increases with age (Malvezzi M, et al. 2016 ), with seldom diagnosis observed before 55 years.

 

Types of Pancreatic Cancer?

Pancreatic cancer is broadly divided into two types, that is:

 

• Pancreatic adenocarcinoma, which comprises 85% of the diagnosed cases and arises from the exocrine glands of the pancreas. This type of pancreatic cancer demonstrates a poor prognosis with a mean 1-year survival after diagnosis exhibited to be only 24%.

 

• Pancreatic neuroendocrine tumor (PanNET), which involves the endocrine tissue of the pancreas and has an incidence of less than 5% of all pancreatic cases(Hidalgo M, et al. 2015). These are relatively slow-growing tumors when compared to adenocarcinoma.

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What Causes Pancreatic Cancer?

The etiology of pancreatic carcinoma is multifactorial in origin, among which cigarette smoking and positive family history of pancreatic cancer are dominant (Klein AP, 2004). About 10% of all pancreatic cancers are considered to be hereditary or familial.

 

Risk factors associated with pancreatic cancer?

Factors that may increase the risk of pancreatic cancer in an individual are divided into two types: these are modifiable and non-modifiable risk factors.

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Modifiable risk factors

Some of the modifiable risk factors include:

 

• Smoking: The increase in the risk of pancreatic cancer is known to be directly proportional to the duration of smoking and the number of cigarettes smoked daily. The risk is nearly recorded to be two times higher in individuals that smoke than in their non-smoking counterparts(Kuzmickiene I, et al. 2013). A meta-analysis published in 2008 reviewed 82 studies that were focused on the association of smoking with pancreatic cancer. They found that the relative risk of developing pancreatic cancer (RR) recorded in all the given literature was 1.74 for active smokers and 1.2 in former smokers. They also concluded that the given risk persisted for at least 10 years even after smoking cessation (Vrieling A, et al. 2010).

 

• Alcohol: high alcohol consumption( more than three drinks daily) is another well-recognized risk factor for the development of pancreatic cancer. A large case-controlled study published in 2010 found an increased risk of pancreatic cancer with consumption of a minimum of 60g/day of liquor (spirits) (Michaud DS, et al.  2010). Another piece of literature found that heavy alcohol consumption significantly amplified the increase of pancreatic cancer risk among active smokers (Rahman F, et al. 2015).

 

• Obesity: high BMI increases not only increases the incidence but also the mortality rates of pancreatic cancer (de Gonzalez AB, 2003). A meta-analysis also confirmed that both general and abdominal obesity are associated with increased pancreatic cancer risk (Aune D, et al. 2012).

 

• Dietary factors: Consumption of red meat cooked at high temperatures, processed meat, fried food, and a diet rich in saturated fats increases the incidence of pancreatic cancer (Lightsey D, 2012). On the other hand, high intake of fresh vegetables and fruits, especially those with high citrus and antioxidant content impart a protective effect, decreasing the risk by 38% and 29%, respectively (Paluszkiewicz P, et al. 2012).

 

• Exposure to carcinogens: exposure to occupational carcinogens is another important etiological factor. These include prolonged contact with pesticides and metalworking such as nickel, cadmium, and arsenic, etc.(Ojajarvi A, 2001).

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Non-modifiable risk factors

 

These include

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• Age: the risk of developing pancreatic malignancy increases with age, with the highest peak observed to be between 60 and 80 years of age(Bosetti C, et al. 2012).

 

• Gender: as previously discussed pancreatic cancer exhibits a slight male predominance.

 

• Ethnicity: literature documents the incidence rate of Pancreatic cancer to be higher in African-Americans than Caucasians, while low incidences are observed in Asian-Americans and Pacific Islanders.

 

• Diabetes mellitus: studies show that pre-existing diabetes is associated with a 1.8-fold increase in the risk of developing pancreatic cancer(Li D, et al. 2011).

 

• Family history of pancreatic cancer: It is estimated that around 5-10% of individuals with pancreatic cancers have a positive family history of pancreatic cancer (Parkin DM, 2011).

 

• Genetic factors: Approximately 10% of individuals with pancreatic cancer demonstrate some associated genetic predisposition, such as BRCA1, BRCA2 mutation, Lynch syndrome, the familial atypical multiple mole melanoma syndromes, Peutz-Jeghers syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome, etc.(Rawla P, et al. 2019).

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Signs and Symptoms of Pancreatic Cancer

The early stages of pancreatic cancer typically do not produce any signs or symptoms. Advanced pancreatic cancer, however, is known to produce signs and symptoms that are non-specific and unexplained. These may include:

• Jaundice with or without pruritus(itching) as usually the most common and often one of the first presenting symptom,

• Light-colored, greasy stools, secondary to malabsorption of fats due to pancreatic enzyme deficiency,

• Dark urine due to increased bilirubin buildup in the body,

• Pain in the upper or middle abdomen and back, due to mass effect from cancer that develops in the body and tail of the pancreas,

• Palpable enlargement of gallbladder and liver,

• Weight loss with no apparent reason,

• Loss of appetite,

• New onset of diabetes,

• Nausea,

• Easy fatigability, etc.

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How Is Pancreatic Cancer Diagnosed?

As priorly mentioned, the detection of pancreatic cancer is fairly difficult in the early onset of the disease due to the late manifestation of symptoms and given deep anatomy of the organ. However, genetic testing is offered to individuals that have a positive family history and high susceptibility to develop cancer.

In routine practice the diagnosis consists of several invasive and non-invasive investigations that are as follows:

 

Medical history and physical exam

The initial most workup is the medical history and examination that occurs when the patient first presents at a physician’s clinic. Here modifiable and non-modifiable risk factors are asked and assessed upon. Jaundice, enlargement of the liver, and gallbladder are examined for and history for pain, weight loss, and appetite are taken. These clues give the physician a rough idea of how to proceed with further investigations.

 

Imaging studies

These include abdominal x-rays, ultrasound, CT scan, MRI, and radiolabelled scans for the detection of cancer. These aid in localizing and estimating the span of the cancer tissue.

 

Ultrasound

Both abdominal or endoscopic ultrasound (US) tests may be employed before proceeding to more advanced imaging.

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Computed tomography (CT) scan:

The CT scan provides detailed cross-sectional images of the abdominal anatomy, particularly of the pancreas in this case. It also reveals any spread of the malignancy in the surrounding organs including the lymph nodes. A CT scan can also help determine if surgery would have suitable outcomes. 

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Magnetic resonance imaging (MRI)

Specialized MRI scans are ordered to accurately localize the malignant cells in a high-risk population. These include:

 

• MR cholangiopancreatography (MRCP), non-invasive imaging that provides detailed imaging of pancreatic and bile ducts. However, sample collection or any therapeutic intervention is not possible with MRCP.

 

• MR angiography (MRA), which accesses the spread of malignancy in the blood vessels. 

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Positron emission tomography (PET) scan

PET scan is a radiolabeled scan that is employed to detect small amounts of cancerous tissue that is not clearly visible on other scans. It helps in detecting distant metastasis when the radioactive dye is taken up by malignant cells present anywhere in the body.

 

Cholangiopancreatography

This is an imaging test where pancreatic ducts and bile ducts are visualized to check if they are blocked, narrowed, or dilated. There are several techniques to perform a cholangiopancreatography such as:

 

• Endoscopic retrograde cholangiopancreatography (ERCP): A technique where the aid of a thin flexible endoscope is employed to track the pancreatic ducts via the gastrointestinal tract. An ERCP has benefits over other previously mentioned studies as it can also be used for the collection of sample biopsy and therapeutic purposes such as the insertion of a stent.

 

• Magnetic resonance cholangiopancreatography (MRCP): previously mentioned in detail.

 

Percutaneous transhepatic cholangiography (PTC):

This invasive imaging is carried out by insertion of a thin, hollow needle through the abdominal wall and directly inserting the contrast medium in the bile ducts. Then x-ray scans are taken to visualize as the dye passes through the bile and pancreatic ducts. Similar to ERCP, this approach can also be employed to take fluid or tissue samples or for the placement of the stent into the bile duct. This diagnostic procedure is only carried out if ERCP cannot be carried out.

 

Blood tests

Several blood labs can be carried out to aid in the diagnosis, such as:

 

• Liver function tests: elevated bilirubin and liver enzymes, although nonspecific but may hint a suspicion of advanced pancreatic disease.

 

• Tumor markers: two common tumor markers have been proposed to be linked with pancreatic cancer. These are CA 19-9 and Carcinoembryonic antigen (CEA). These markers usually facilitate in detecting the response of treatment and recurrence of malignancy.

 

• Other blood tests: Other tests, like complete blood tests, kidney function tests, and bone marrow function tests, etc, can be further ordered before initiating the treatment plan.

 

What Treatments Exist for Pancreatic Cancer?

Unfortunately, no single treatment modality has been yet found to be curative in the case of pancreatic cancer. The standard regimes currently include surgery, chemo, and radiotherapy, palliative care, along with some new advancements that are in trials.

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Surgery

One of the following types of surgical procedures may be employed to resect pancreatic cancer. 

 

Whipple procedure:

Whipple procedure is the commonest surgical technique that is employed for the recession of tumors involving the head of the pancreas. This major operation involves the removal of the head of the pancreatic and the curve of the duodenum together, commonly termed as pancreatoduodenectomy. Two bypasses are thus created to connect the stomach to the jejunum called a gastro-jejunostomy and the jejunum to the cystic duct to drain bile called cholecysto-jejunostomy. Being a high-risk surgery it is only offered to individuals that can withstand the procedure and if the cancer is localized without any invasion or metastases. Often removal of the spleen and lymph node is also carried out prophylactically to reduce the risk of remission.

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Distal pancreatectomy

This procedure is offered when pancreatic cancer involves the tail of the pancreas. Often resection of the spleen called the splenectomy is carried out as it shares a common blood supply.

 

Both the surgical procedures have a high complication rate, with the most common being delayed emptying of the stomach(Wolfgang CL, et al.2013).

 

Radiation therapy

Radiation therapy is recommended in cases of unresectable cancers and as adjuvant therapy in cases where surgery alone is unable to achieve a cure. External radiation therapy reduces the cancer mass alongside disrupting the blood flow towards the malignant tissue.

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Chemotherapy

Chemotherapy can either be offered as a neoadjuvant (before surgery), adjuvant (after surgery) or alone as a separate therapy in cases of advanced non-resectable pancreatic cancer. Commonly a combination therapy is preferred over a single-drug regimen. Some of the common chemotherapy drugs used in pancreatic cancer are Gemcitabine (Gemzar), Oxaliplatin (Eloxatin), 5-fluorouracil (5-FU), Capecitabine (Xeloda), Cisplatin, Irinotecan (Camptosar), and Albumin-bound paclitaxel (Abraxane), etc.

Some common potential side effects of these drugs include nausea, vomiting, loss of appetite, mouth ulcers, hair loss, diarrhea, and constipation, etc. Some of the specific side effects related to individual drugs are peripheral neuropathy observed with cisplatin, oxaliplatin, and paclitaxel, kidney damage, and auditory complaints with Cisplatin, etc.

 

Palliative care

In cases where the cancer is found unresectable completely, certain limited surgical procedures may be offered to ease the symptoms and improve the quality of life. These include:

 

Biliary bypass:

In instances where the cancer is obstructing the biliary outflow tract, a bypass may be created to drain the bile. This is done by anastomosis of the gallbladder or the bile duct directly with the intestine.

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Endoscopic stent placement:

Another interventional technique to drain the gallbladder is the placement of a stent in the bile duct that keeps the lumen open.

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Gastric bypass:

Similar to the biliary bypass, gastric bypass can also be created between the stomach and small intestine, if the tumor causes mass effect obstructing its outflow.

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Prognosis of pancreatic cancer

Several factors influence the survival outcomes in pancreatic cancer. These may include relatively low-risk factors, age, the response of cancer to treatment, tumor grade, and levels of tumor marker CA19, etc.  According to the American Cancer Society, the SEER database records a mean 5-years survival rate of 39% for localized pancreatic cancer and only 3% for cancer with distant metastasis.

 

 

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