Overview Of Pancreatic Cancer Biology Essay

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The role of imaging is very important in the diagnosis and management of patients with pancreatic cancer. Different imaging modalities aids in these diagnosis and management. Some of these modalities involve ionisation radiations such as computed tomography (CT), whiles others like ultrasound (US) and magnetic resonance imaging (MRI) does not involve ionisation radiation. (Howlett & Ayres 2004). Various modalities can be used to image the pancreas. Imaging can be done non- invasively through CT, US and MRI or invasively through endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). These imaging modalities can be either combined or used alone in the diagnosis and staging of pancreatic cancer.( Sahani, Shah, Catalano, Boland,& Brugge,2008).

The pancreas is an exocrine and endocrine gland situated behind the stomach in the epigastric region of the abdominal cavity. It has the head, body and tail as its main body parts with the role of producing pancreatic enzymes to aide digestion. (Martini & Nath, 2009). Blood supply to the pancreas is by the splenic, mesenteric and pancreaticoduodunal artery, whereas venous drainage is by corresponding veins. (Tortora & Derrickson, 2009).

Several diseases affect the pancreas such as pancreatitis, cystic tumours and pancreatic carcinomas. (Underwood, 2004). Pancreatic carcinomas, mostly adenocarcinomas has majority of the tumours occurring in the head of the pancreas. Aetiology is unknown although it's linked with cigarette smoking, diabetes mellitus, and a diet rich in fat and protein. (Levison,Reid, Burt, Harrison,& Fleming 2008). Carcinomas in the head of the pancreas can block the common bile duct causing obstructive jaundice whereas carcinomas in the body and tail of the pancreas are asymptomatic until its spread to other organs. The spread of pancreatic adenocarcinomas can be through the blood to the liver and through the lymphatic to the surrounding lymph nodes. Patients with suspected pancreatic cancer normally present with weight loss, epigastric abdominal pain and jaundice. Prognosis of pancreatic carcinomas is very poor as diagnosis mostly occurs after metastatic spread. (Underwood & Cross 2009).

Imaging modalities deemed appropriate by the royal college of radiologist (RCR) guidelines for diagnosis and investigating of pancreatic cancer are US and CT, whereas for further or specialised investigation should include MRI, magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP). (RCR, 2007). The RCR guidelines also suggest that US, CT and MRI is relevant in the staging process of pancreatic cancer. (RCR, 2007).

As earlier mentioned, US, is one of the modalities that does not use ionisation radiation. Images of US are produce by echoes of high frequency sound waves reflected from body surfaces. (Gibson and Mitchell 2009). When US scanning is been performed, images are obtained in real time, which gives good indication of blood flow and any solid mass. It is also good in differentiating between cystic and solid masses.(Chowdhury, Wilson, Rofe,& Jones, 2010).

Additionally, the cost of US is reasonably low, the equipment can be easily transported and it is a non-invasive scanning. However, US scanning can take longer and the quality of the image depends on the operator and the amount of fat on the patient. Also, some parts of the organs can be obscured by bowel gases and bones which reduce the area of view.(Chowdhury, Wilson, Rofe,& Jones, 2010).

Patients presenting with epigastric pain, weight loss and jaundice are initially prescribe transabdominal US as the first modality to examine the pancreas. This is because, US is able to assess and accurately evaluate the biliary tree, hepatic parenchyma and show any ascites as well as show any pancreatic mass. (Howlett & Ayres 2004). According to Stocksley(2001), US has a sensitivity of 90-98% in detecting pancreatic mass. Hence it should be the initial point of contact for diagnosis of suspected pancreatic carcinomas. CT on the other hand is useful when pancreatic malignancy is suspected, as it will show pancreatic mass and gives indication that makes the pancreas unresectable such as liver or lung metastases, arterial or venous blood connection to the tumour, and any pressure to surrounding structures by the tumour. (Howlett & Ayres 2004). Similarly, MRI is also very accurate in predicting if a pancreatic tumour is unresectable as it evaluates the pancreatic duct and parenchyma, surrounding soft tissues and blood network to the pancreas. ( McSweeney, O'Donoghue, Jhaveri,2010).

That said, before any US examination is performed, the patient needs to be prepared by not eating for four to six hours prior to the examination. This is to ensure that the gall bladder is distended and bowel gas reduced. (Dogra & Rubens, 2004).

Similarly, a good view of the pancreas during a transabdominal scanning can be achieved by using a low frequency curved array probe which provides significant penetration of deeper structures. Also, taking transverse and sagittal views at an oblique angle to the xiphoid gives a good visualisation of the pancreas.(Lowy, Leach, Philip, 2008).

When the tumour is visualised on US, it appears as hypoechoic focal mass with irregular margins. There is also the dilatation of both the pancreatic and common bile ducts. (Lowy, Leach, Philip, 2008).

Schima et. al., (2007) however suggest that transabdominal US alone is not efficient enough to show small pancreatic tumours and the extent of spread of the disease. Therefore, endoscopic ultrasound (EUS) is advised in the detection of small tumours, extent of spread and in guided biopsies. EUS is an endoscope connected with ultrasound at the end. (Willet, Czito, Bendell &Ryan, 2005).

The device, when put through the stomach can show any lesions in the body and tail of the pancreas, as well as give detailed evaluation of the pancreatic parenchyma and adjacent structures. It is also useful in the sense that, it can show the pancreas from the stomach or the duodenum. (Choi, et.al. 2010). Similarly, it will also demonstrate any mass in the head of the pancreas when imaging the duodenal wall. It also gives magnified images of the pancreas and local blood vessels. (Yang,Wagner, Fuss and Thomas 2005).

According to Santo (2004), EUS has 90% and 99% sensitivity in detecting pancreatic tumour and tumours less than 3cm respectively, whereas CT has 55% sensitivity. It goes on to add that EUS has a 97% sensitivity compared to 73% sensitivity of helical CT in detecting pancreatic tumours. Schima et.al., (2007) supports this by confirming that even in multi detector CT (MDCT), EUS is superior in detecting small tumours as it has a sensitivity of 98% compared to 86% of MDCT.

Additionally, with tumours smaller than 25mm, Garcia, Noia and Munoz (2009) states that EUS has a sensitivity of 89% compared to 53% of MDCT. Similarly, EUS had a sensitivity of 93% and 90% compared to 53% and 40% of CT and 67% and 33% of MRI in detecting tumours less than 3cm and 2cm respectively. (Garcia, Noia and Munoz, 2009). This depicts that EUS is better equipped in detecting smaller pancreatic tumours than CT and MRI.

Another benefit of EUS is in guided biopsy. According to Boujaoude,(2007) when a pancreatic tumour is considered unresectable by CT or MRI, EUS guided fine needle aspiration (FNA) biopsy is done as a follow up. EUS guided FNA biopsy is when a histological sample is taken from a pancreas to confirm the presence of pancreatic tumours. It also determines whether the sample is benign or malignant. (Boujaoude, 2007).

EUS-FNA biopsy is done prior to chemotherapy or treatment and according to Boujaoude, (2007) EUS-FNA has a sensitivity of 75% to 90%, a specificity of 82% to 100% and an accuracy of 85% in diagnosing pancreatic tumours.

Garcia, Noia and Munoz (2009), supports this by saying EUS guided FNA has a sensitivity of 90% for malignancy compared to the negative results in CT guided FNA. They further states that the sensitivity, specificity and accuracy in diagnosing pancreatic tumours using EUS guided FNA is 84.3%, 94% and 84% respectively. As earlier mentioned, apart from EUS-FNA showing if a lesion is benign or malignant; it helps in making definitive diagnosis, which enables necessary treatment to commence. (Garcia, Noia and Munoz 2009).

CT, unlike US, uses ionisation radiation and cross sectional images are produced when several radiation detectors receive transmitted x-rays beam from an area of interest of a patient. The data received is converted digitally into a computer. (Gibson and Mitchell 2009). Images from CT unlike US are not obscure by bowel gas or body fat, scanning is quick and non -invasive. CT can also give good contrast range and detailed organ structures, as well as images can be reconstructed in three dimensional formats. Setbacks of CT scanning include its high radiation dose, contrast allergies, expensive and not portable compared to US machines. (Chowdhury,Wilson,Rofe,Jones, 2010).

According to Schima et al.,(2007) CT with contrast is the suitable method for detection and staging of pancreatic cancer with Images acquired in arterial, hepatic and pancreatic phases. That said, when a patient presents with unspecific abdominal pains, such painless jaundice, CT screening can be performed. This is when 5mm thick slice from the diaphragm to the pelvis is scanned with contrast in portal venous phase to make sure that there is no metastatic spread, common bile or pancreatic duct dilatation. (Lowy, Leach,& Philip, 2008).

Prior to scanning a patient with suspected pancreatic metastases, 800ml of water is given to the patient 30 minutes before scan to drink and a further 300ml just before scanning commence. The oral contrast aids in assessing the pancreatic head, duct, and distal common bile duct. It also gives good depiction of the duodenal wall. (Bruening, Kuettner &Flohr, 2006).

Scanning is done with intravenous (IV) contrast in the arterial, pancreatic and hepatic phase. The IV contrast is relevant in the evaluation of malignancy and useful in tissue differentiation. It is given by the help of a power injector at a rate of 4mL/s in a rapid dose. (Lowy, Leach, Philip 2008).

The landmarks for scanning of suspected pancreatic tumour in CT is from the xiphoid to the iliac crest. The arterial phase which is relevant is evaluating the anatomy of the arteries begins 20-30seconds after contrast injection. It is followed by the pancreatic phase at 40-50seconds after injection. The pancreas in this phase is cut axially into thin slices and this gives a detailed attenuation difference between the tumour and gland. The hepatic phase at 60-70 seconds delay is useful in assessing metastatic spread to the liver. (Lowy, Leach, Philip 2008).

On a CT scan image as shown below, a pancreatic tumour will show up as hypodense, with dilation of both common bile duct and pancreatic duct. It can also show a decrease in pancreatic tissue, and an enlargement of the pancreas due to its subtle nature. (Webb, Brant, Major 2006).

Below is a pancreatic phase CT image showing a hypodense pancreatic lesion in the head of the pancreas. (Arrowed).

schima et al.,(2007).

Aside it's higher resolution and quicker image acquisition, MDCT according to McSweeney, O'Donoghue, Jhaveri, (2010), is the modality of choice when evaluating pancreatic cancer. This is because it can provide detailed staging, assessment, detection and tumour resectability as well as differentiate pancreatic adenocarcinomas from intraductal tumours. The sensitivity of MDCT according to Schima et al. (2007) in detecting pancreatic cancer is 100% compared to 82-94% of gadolinium MRI scan.

When a CT scan is evaluating a pancreatic tumour for its unresectability, it takes into account peritoneal involvement, extent of local invasion, distant metastases, malignant ascites and if the encasement of the vessels is greater than 50%. If all these criteria are met, then the tumour is unresectable. (Lowy, Leach, Philip, 2008).

Francis (2003) confirms CT to be superior in detecting tumours which are unresectable with more than 90% accuracy than MRI.

MRI, according to Longmore, Wilkinson and Rajagopalan,(2004), operates when radiofrequency pulse at its highest frequency is used to disturb hydrogen atoms in a strong magnetic field. Signal detected when the hydrogen atoms are returning to equilibrium are used to produce an image.

Whereas other modalities like CT and US relies on the soft tissue density and tissue echogenicity respectively to generate contrast, MRI differs by depending on many properties. MRI relies on the proton density in a tissue and weather the hydrogen atoms are bound by fat or in free water. It also depends on the blood or cerebrospinal fluid flowing through the tissue and the T1 and T2 relaxation times. (Lisle, 2007).

T1 and T2 are the basic image sequences performed during MRI examination.(Lisle, 2007). In a T1 weighted image, fluid appears dark and fat bright. T1 is good in showing anatomical details whereas T2 is good at showing pathology, especially oedema related pathologies. This is because it shows fluid as bright and fat dark. (Longmore, Wilkinson,& Rajagopalan, 2004).

MRI can be produced in any plane with a three dimensional data acquisition. MRI is excellent in imaging soft tissues and gives better soft tissue contrast than CT. It is also highly sensitive in detecting range of pathology. (Howlett & Ayres 2004). Similarly, angiography can be performed with MRI without the use of contrast by using by a technique of two dimensional (2D) time of flight. (Lowy, Leach, Philip, 2008).

MRI is disadvantage in terms of its motion artefacts, high cost, unavailability and longer scanning time compared to CT. it is also not recommended for claustrophobics, patients with pacemakers, hearing aids and metal works due to its strong magnetic field. (Chowdhury,Wilson,Rofe,Jones, 2010).

During an MRI scan of pancreatic carcinoma, oral contrast is not always given as in CT. This is because it can take out the intensity of the T2 signal in the stomach and small bowel, making depiction of the biliary tree difficult. (Balthazar, Megibow & Mucelli, 2009).

MRI sequences performed for pancreatic tumours are T1 weighted fat suppressed and gadolinium enhanced gradient recall echo (GRE). In the former sequence, pancreas will depict high signal intensity due to its protein content whereas tumour will show low signal intensity. The latter sequence however, shows the enhancement of pancreatic tumours to be less than the surrounding parenchyma. (Francis, 2003).

That said, according to Lowy, Leach, Philip, (2008), the introduction of new contrast mangafodipir trisodium has improved the detection of lesions in the pancreas and liver as the contrast is taken up by the normal parenchyma of the pancreas and the hepatocytes. Francis (2003) confirms this by adding that, mangafodipir trisodium enhanced MRI is superior in the detection of tumours and metastases and accurate in the staging than enhanced CT.

Additionally, MRI can be combined with magnetic resonace cholangiopancreatography(MRCP) in secretin enhanced imaging. Secretin is a hormone that will cause the pancreatic duct to distend by stimulating its secretions. When this happens, it causes the delineation of the pancreatic duct and its side branches to improve. (Sahani, 2007).

The appearance of pancreatic tumour on an MRI image is similar to that of CT. The tumour appears hypointense, focal mass, and atrophy of pancreas as shown below.

T1 weighted GRE gadolinium enhanced image showing a tumour in the tail of the pancreas(arrowed) with a low density than the surrounding organs.( Schima et al.,2007).

(schima et al., 2007).

In a study conducted by Tapper et.al, (2010), they found out MRI is very essential in preoperative imaging as it is has a sensitivity, specificity and accuracy of 100%, 73.2 -78.9%, 86.3-87.5% respectively in showing if a tumour is resectable.

However, when it comes to tumour unresectability, MRI has an accuracy of 85% compared to the 90% of CT. (Lowy, Leach, Philip, 2008)

On the other hand, MRI is able to accurately detect at a 95% and 95.9% venous and arterial connections with tumours respectively. This helps to know the extent of metastatic spread, especially to the liver. It is also highly sensitive in disclosing liver metastasis and lesions compared to EUS and CT. ( Neoptolemos, Urrutia, Abbruzzese & Buchler, 2009),

Staging of pancreatic adenocarcinomas is described by the TNM (tumour, nodular and metastatic) stages. T stage which is concerned with the size of the tumour and its spread to local organs is subdivided into T1 to T4. At T4, the tumour has invaded surrounding organs such as the stomach and spleen. The N stage looks at metastasis in the peri pancreatic lymph node whiles the M stage looks at any distant metastases, mostly to the liver. (schima, et al., 2007).

Pancreatic cancer has a poor prognosis and as a result is one of the highest causes of cancer related deaths. The only treatment present is Resection of the tumour through surgery and followed with chemotherapy. Survival after resection is dependent on metastatic spread.(Lillemoe, Yeo, & Cameron, 2000). That said adjuvant radiation therapy which according to Lillemoe, Yeo and Cameron (2000) can prolong the life span of patients who have undergone tumour resection.

Technology in MRI is advancing in such a way that, there is the introduction of phased array multiple coils which improves signal to noise ratio and increased area of coverage. Other future development includes combining other modalities with MRI such as CT and PET. This new development will work on the idea of using the high sensitivity and resolution of MRI together with the faster imaging ability of CT to examine patients. (Westbrook, Roth, & Talbot, 2005).

Similarly, there is the development of multi detector CT such as 256MDCT. This will provide detailed and higher spatial resolution without a significant increase in radiation dose. (Nightingale and Law 2010).

Several studies have discussed the superiority of EUS, MRI and CT in imaging pancreatic cancer. However, from the discussions, it is evident that all the imaging modalities are relevant in the imaging and management of pancreatic cancer. EUS-FNA is useful in confirming whether a pancreatic tissue is benign or malignant for treatment to commence after CT has confirmed its unresectability. EUS also has a high sensitivity in detecting small tumours. CT on the other hand is very useful in the staging, and accurately detecting unresectable tumours with a sensitivity of 90%. It is also valuable in detecting the extent of tumour spread. Finally, MRI also has the ability to detect a resectable tumour and has the added benefit of MRCP in secretin enhanced imaging. It also has the ability to use angiography to evaluate vascular involvement which makes MRI also significant in the imaging and management of patients.