Pancreatic Cancer - "The Forgotten cancer"

People used not to talk about pancreatic cancer - and more worrying medical professionals and health care providers had a nihilistic attitude to treatment due to lack of effective options. However that is changing and it is important that the public and medical professionals are aware of the disease, its symptoms and treatment options. Nihilism is out of date and needs to be replaced by a determination to improve outcome.

There are about 7000 cases of pancreatic cancer a year and a similar numbers of deaths. However progress is being made with trials showing adjuvant chemotherapy providing 21% 5 years survival (ESPAC-1 ) and locally advanced patients getting 24-26% 1 year survival in trials of combination chemotherapy (eg Gem-Cap).

Some patients can do very well so it is important that they get speedy access to the best possible care. This applies to inoperable as well as operable patients; young, elderly (eg in their 80s) or those with metastatic disease can live 18months or more - see the Pancreatic Cancer UK web-site for some patient biographies. It should also be born in mind that 20% of patients presenting with tumours in the head of the pancreas have diagnosis other than the aggressive ductal adenocarcinoma, eg ampullary or neuroendocrine tumours, with much better prognosis.

There is now incontrovertible evidence that outcome is improved by management in a specialist centre. There are now proven treatments to improve quality of life and survival. The major stumbling block remains the delay in diagnosis and referral.

Diagnosis is traditionally considered hard with no obvious early symptoms or nonspecific symptoms when they do occur - but is that really the case? We must start to tackle this. Too many patients are diagnosed too late and die within days or weeks without treatment. A few key points to remember may help for example:

• Jaundice is always an urgent referral
• Pancreatic cancer should be excluded in patients over 50 with new diabetes, if they are not obese and have no family history
• Watch out for signs of exocrine pancreatic insufficiency such as pale, floating, fatty stools and diarrhoea
• Not all patients are old - watch out for the 30-50 year olds
• Watch out for persistent back pain - constant, nagging pain, worse lying down, eased by bending forward and sleeping in sitting position
• Watch out for family history of pancreatic cancer, pancreatitis, familial cancer syndrome
• Smoking is a risk factor but only in about 30% of cases
• Chronic pancreatitis is a risk factor
• Not all patients get all symptoms eg some have sudden painless jaundice others severe abdominal or back pain or IBS like symptoms over a period of time and no jaundice
• Unexplained upper abdominal pain and weight loss, with or without back pain, or an upper abdominal mass without dyspepsia are also cases for urgent referral for suspected cancer

• Standard diagnostic technique is abdominal ultrasound but that can miss early, small operable tumours. CT is better
• Blood tests should be done for anaemia, clotting profile, liver function and proteins
• Serum cancer antigen (CA) 19-9 is a good tumour marker but is artificially elevated in the presence of obstructive jaundice and chronic pancreatitis and isn't raised in all panceratic cancer patients.

You need to be aware of the Improving Outcomes Guidance for Upper GI cancers , NICE referral guidelines for suspected cancer, Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut. 2005. You need to ensure that a local regional centre for pancreatic cancer has been designated, has been financed by the local PCTs to cope with the extra case load and to ensure high quality services consistent with IOG. You need to be aware of the local referral guidelines.

Symptoms of pancreatic cancer include:

Painless jaundice, pruritus secondary to jaundice, fatigue, weight loss, back pain (constant, nagging, worse lying down, eased by bending forward and sleeping in sitting position), vague dyspepsia or abdominal discomfort, anorexia, constipation (reduced food intake), steatorrhea (fatty stools), late onset diabetes mellitus without risk factors for diabetes, acute pancreatitis of unknown cause, chronic pancreatitis, acute cholangitis, vomitting due to duodenal obstruction, deep-vein thrombosis

Signs include: jaundice, scratch marks secondary to jaundice, multiple bruises (ecchymoses) secondary to impaired clotting, hepatomegaly, palpable gallbladder - Courvoisier's sign, cachexia, left supraclavicular (Virchow's) node enlargement - Troisier's sign, anaemia, abdominal mass, metastasis at the umbilicus - Sister Joseph's sign, ascites, venous gangrene of the lower limbs, migratory thrombophlebitis

The functioning neuroendocrine tumours may have symptoms related to the particular hormone that is being over-expressed. However nonfunctioning neuroendocrine tumours will only have the common pancreatic cancer symptoms.

Screening for high risk groups, especially hereditary, is becoming a real prospect and work in this area is co-ordinated by EUROPAC at Royal Liverpool University

Research is ongoing to find biomarkers for use in screening and diagnosis. Pancreatic Cancer UK is planning work to investigate the history of patients' symptoms to see if more specific guidance can be produced.

Once the patient has been diagnosed you need to be aware of complicating factors:

• DVT is a particular complication resulting in death before treatment.
• Pain control can be hard but coeliac plexus blocks and bilateral transthoracic sympathectomy are options as well as opiates and chemotherapy.
• Stents used to relieve jaundice can block naturally and this does not mean disease progression - recurrence of jaundice after stent placement is an indication for urgent referral for stent change. Need to avoid life threatening infection, inpatient treatment and treatment interruption due to blocked stent. Plastic stents will need to be routinely replaced. Metal stents are preferred due to longer life.
• Inoperable as well as post-surgical patients are likely to benefit from use of pancreatic enzyme replacement therapy.

Finally

• All patients should be encouraged to enter trials

• Don't let patients die of jaundice

• Beware the thin, late onset, diabetic

• Back pain isn't always benign

• Don't forget pale, floating, fatty stools

• Is it really IBS?

• Come to PCSG Annual Scientific Meeting on 13th October to learn more about the current state of the art in pancreatic and other GI cancers

Pancreatric Section, British Society of Gastroenterology; Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland; Royal College of Pathologists; Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut. 2005 Jun;54 Suppl 5:v1-16.

Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours Gut 2005 Jun; 54 (Suppl 4) : 1-16.

National Cancer Institute (USA) - Pancreatic Cancer Treatment

Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Buchler MW; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18; 350(12):1200-10. Erratum in: N Engl J Med. 2004 Aug 12;351(7):726.

Guidance on the use of gemcitabine for pancreatic cancer NICE Technology Appraisal #25 (2001)

Guidance on commissioning cancer services: improving outcomes in upper gastro-intestinal cancers the manual 2001 product code 23018 Department of Health

NICE Referral guidelines for suspected cancer 2005 CG027

ESPAC-3(v2) Phase III Adjuvant Trial in Pancreatic Cancer Comparing 5FU and D-L-Folinic Acid vs. Gemcitabine. Leeds, UK: National Cancer Research Network Trials Portfolio, 2004

Phase III randomised comparison of gemcitabine (GEM) versus gemcitabine plus capecitabine (GEM-CAP) in patients with advanced pancreatic cancer ECCO abstract 2 Nov 2005, D. Cunningham, I. Chau, D. Stocken, C. Davies, J. Dunn, J. Valle, D. Smith, W. Steward, P. Harper, J. Neoptolemos

Pancreatic Cancer UK

CancerStats Pancreatic Cancer - UK

Fast Facts: Diseases of the Pancreas and Biliary Tract, John P Neoptolemos and Manoop S Bhutani

EUROPAC europac@liv.ac.uk