Pancreatic adenocarcinoma is the most common form of pancreatic cancer and a major cause of cancer related death.
They arise from the ductal epithelium as the result of accumulated genetic mutations. Adenocarcinomas are the most common pancreatic neoplasm, accounting for around 85% of cases.
Asymptomatic through much of its development, sadly this cancer is commonly diagnosed at a late stage when the chance of cure is faint. When caught early, surgery may offer a chance at curative therapy.
There are approximately 10,300 cases of pancreatic cancer each year in the UK.
Overall it is the tenth most common cancer in the UK, though is the fifth most common cause of cancer death.
In 2017 it was the ninth most common cancer (5,000) in females and the twelfth most common (5,300) in men in the UK. Incidence is highest in those aged 85-90 with around 47% of cases occurring in those above the age of 75.
Pancreatic cancer appears to affect those of black and white ethnicity more than those of asian ethnicity.
A number of risk factors are associated with the development of pancreatic cancer.
Genetics may play a significant role in the development of pancreatic cancer. Those with two first degree relatives affected have an 18 times increased relative risk of developing pancreatic cancer. Those with hereditary pancreatitis with a PRSS-1 mutation are at 50 times increased risk.
Our understanding of the pathogenesis of pancreatic adenocarcinoma continues to develop, though it remains incomplete.
It is thought that many adenocarcinomas arise from precursor lesions - pancreatic intraepithelial neoplasia (PanIN). Three grades of PanIN exist, with progressively increasing dysplasia and in some cases eventual invasive pancreatic adenocarcinoma. KRAS mutations are almost ubiquitous in PanINs and as the grade increases mutations are often found in p53, CDKN2A and SMAD4 tumour suppressors.
Pancreatic adenocarcinoma can also develop from cystic neoplasms. These include intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasia.
Around 70% of cases arise from the pancreatic head whilst 20% originate in the body/tail. The remaining cases may affect the entirety of the pancreas.
Metastatic spread is common at diagnosis. Spread often affects the liver, lungs and peritoneum.
Features of pancreatic cancer include abdominal pain, jaundice and unexplained weight loss.
Pancreatic cancer may be asymptomatic for much of its development, becoming symptomatic in later stages of the disease. A significant minority of cases are diagnosed incidentally on imaging organised for unrelated reasons.
The clinical features may reflect the underlying tumour location. Tumours affecting the pancreatic head more often present with jaundice, weight loss and steatorrhoea.
The onset of diabetes can somewhat rarely be a sign of pancreatic cancer. However the true nature of this relationship (causative vs result of etc) is still being established.
Presenting features may be the result of spread of disease. Spread most commonly affects the liver, lungs and peritoneum.
Features may include an abdominal mass, ascites and lymphadenopathy (Virchow’s node). Rarely a Sister Mary Joseph node (palpable nodule at umbilicus caused by metastatic spread of an abdominal or pelvic cancer) may be seen.
Surveillance should be offered in certain individuals at increased risk of pancreatic cancer
Surveillance is advised for patients who are at increased risk of pancreatic cancer. NICE guidance NG85: Pancreatic cancer in adults: diagnosis and management, advises surveillance for those with:
NICE also recommend considering surveillance if:
Surveillance generally takes the form of MRI/MRCP or EUS for those without hereditary pancreatitis and CT (pancreas protocol) for those with hereditary pancreatitis.
The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) is a screening study looking at pancreatic cancer in those with genetic risks.
The entry criteria, taken from the study site are:
Screening may involve blood tests (fasting glucose and CA 19-9), imaging (EUS and CT) and in the future molecular tests (samples obtained by OGD).
Depending on the presentation, the first investigations tend to be either an USS, CT or MRI.
Vitamin D deficiency is common and may be screened for. Some centres are investigating the use of DDIMER as an indicator of metastatic disease.
An urgent cancer referral for suspected pancreatic adenocarcinoma should be considered in patients >40 years old with new-onset jaundice.
The NICE clinical guideline 12 (NG12) has recommendations for urgent referral in patients with suspected pancreatic cancer. This includes patients who are > 40 years old with new-onset jaundice. The presence of painless jaundice is more concerning for malignancy.
An urgent CT of the abdomen (within two weeks) should be considered in patients aged > 60 years old with any of the following features:
In certain situations, it may be more appropriate to advise urgent admission via accident and emergency if the patient is acutely unwell, particularly if there are any features of biliary infection due to an obstructed biliary system.
A biopsy may be used to confirm a diagnosis of pancreatic adenocarcinoma.
Patients will tend to have a suspicious lesion on CT, MRI or USS, but biopsy allows for confirmation. Some patients who underwent ERCP at their initial evaluation may already have histology or cytology.
Pre-operative biopsy confirmation is NOT necessarily required prior to surgery in those with resectable disease. These decisions are complex and taken by specialist MDTs. There are two main biopsy techniques are:
Pain control, nutrition and emotional well-being are all key to holistic management of patients.
The diagnosis of pancreatic cancer places a huge psychological burden on the patient and their loved ones.
Input from multiple specialist are needed. Clinical nurse specialists act as a contact point, and follow the patient through their journey, providing emotional support as well as information on their condition and management.
Palliative care input may be required, even in those with potentially curative disease, for help, information and management of symptoms.
The extent of pain experienced by patients is highly variable. Simple analgesia like paracetamol may need to be complimented by opioid analgesia. In those with uncontrolled pain coeliac plexus block may be considered.
It is important to be aware some symptoms such as abdominal cramps may represent exocrine insufficiency and require replacement.
All patients require nutritional assessment. Malnutrition is common and may occur for a multitude of reasons including the metabolic burden of the tumour, nausea and anorexia and pancreatic exocrine insufficiency.
There is evidence that oral enzyme replacement improves outcomes and as such most patients are offered replacement therapy (e.g. CREON).
A healthy balanced diet should be maintained and dietician referral organised where needed.
When diagnosed early, resection may allow for disease remission.
The decision to treat disease as resectable should be made at specialist MDT. Around 15% are resectable at time of diagnosis.
In general disease is resectable (based on NCCN criteria) if:
It may not be until time of surgery that disease is found to be non-resectable. Borderline resectable disease refers to partial involvement, encasement or abutment of key vessels - this will not be covered in detail in this note.
In patients with biliary obstruction and resection is possible, this is preferred over preoperative biliary drainage in those with resectable disease. Ideally these patients should be ‘fast-tracked’ to surgery.
In those likely to have a delay in surgery or in whom it is not feasible - ERCP may be used to allow drainage.
NICE advises neoadjuvant therapy is only used in the setting of a clinical trial in patients with resectable / borderline resectable disease.
When used options include chemotherapy (e.g. FOLFIRINOX or gemcitabine-based regimens), chemoradiotherapy and stereotactic radiotherapy.
Resection options include:
At the time of surgery, disease may be found to be unresctable and the primary operation abandoned. Biliary bypass or gastrojejunostomy may be performed.
The spleen is commonly removed in surgery for pancreatic cancer. This places the patient at increased risk of infection that is lifelong but most significant in the first 2-3 years. Patients undergoing splenectomy require (for adults):
Chemotherapy is considered as adjuvant therapy in all patients. Timing is dependent on patient factors and recovery from surgery. Regimens include:
Disease not amenable to resection may be managed with chemotherapy and at times radiotherapy.
Palliative care input, particularly for pain management is important. Psychological support and counselling should be offered where appropriate or requested.
Unresectable disease (based on NCCN criteria) may be defined as:
Metastatic disease is defined as evidence of distant disease spread.
Systemic combination chemotherapy is offered to those with locally advanced disease who are able to tolerate it.
Gemcitabine may be considered as an alternative in those not tolerating combination therapy.
Systemic chemotherapy is the mainstay of management. FOLFIRINOX may be given to those with an ECOG performance status of 0–1.
In those not well enough for FOLFIRINOX, gemcitabine combination therapy or gemcitabine alone may be considered.
Oxaliplatin based chemotherapy may be used as a second line option.
Radiotherapy may be used in those with unresectable disease. Use is guided by the specialist MDT and oncology. Forms include palliative radiotherapy, chemo-radiation or stereotactic radiotherapy.
The prognosis is related to staging at presentation, however overall survival is poor.
Statistics for median survival vary widely depending on the study used. For pancreatic cancer overall, Cancer Research UK estimate that around 25% of patients survive one year or more. Only 7% survive for 5 years or more.
Those with the earliest stage disease (stage I) have a median survival of approximately 20 - 25 months. Those with stage IV disease (metastatic) have a median survival of around 4.5 months.
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