Pancreatic cancer refers primarily to adenocarcinomas – specifically ductal adenocarcinoma which account for > 85 % of all pancreatic neoplasm. Pancreatic adenocarcinoma- most common and arises in exocrine glands of the pancreas. Pancreatic neuroendocrine tumour -Less common ( < 5 % and occurs in the endocrine tissue of pancreas )
Epidemiology-Pancreatic cancer is not rare and the incidence of pancreatic adenocarcinoma ( hence mentioned as pancreatic cancer Pan-Ca here ) is rising in the developed world Seventh leading cause of global cancer deaths in industrialized countries 11 th most common cancer in the world 458,918 new cases in 2018 and causing 432 ,242 deaths ( GLOBOSCAN 2018 ) 367,000 new cases in 2015 and 359,000 deaths in same year Slightly more common in men Most common presentation is from 65-75 yrs age with painless obstructive jaundice and weight loss ( seldom diagnosed before 55 yrs age ) Highest incidence in Europe and N America and lowest in Europe and S Central Asia
Why important- Extremely poor prognosis – due to several factors as ○ usually diagnosed at an advanced stage ○ no clinically useful markers for early detection ○ patients seldom exhibit symptoms until an advanced stage of disease hence late diagnosis ○ Anatomy- close proximity to major blood vessels -tumour invades and spreads ○ Available diagnostic tests are non specific and may miss patients with early stage disease ○ Pan-Ca is remarkably resistant ( or tolerant ) to most conventional treatment options including chemotherapy , radiotherapy and molecular targeted therapy ○ Pan-Ca harbors multiple genetic and epigenetic alterations and have complex and dense tumour microenviornments ○ Population screening is not considered useful to detect the disease at an early stage ( low lifetime risk < 1 % ) Up to a staggering 48 % of the diagnosis is made following an emergency admission ○ over 40 % of patients visit their GP x 3 times or more before even being referred to hospital ○ 16 % have to visit their GP or hospital 7 times or more before the correct disgnosis is made One year survival is around 20 % and 5 year survival rate is under 7 % – this figure has not improved in around 40 yrs !
Risk factors- non-modifiable Age Sex Ethnicity Blood group shown to be associated with different ABO blood groups patients with blood gr A , AB ,or B at higher risk Gut microbiota Family history and genetic susceptibility- 5 to 10 % of cases e.g hereditary breast/ ovarian cancer , familial atypical mole melanoma , Peutz-Jegher’s syndrome , hereditary non-polyposis colorectal cancer syndrome ( Lynch syndrome ) Mutations in BRCA2, BRCA1 , CDKN2A, ATM , STK11 , PRSS1 , MLH1 & PALB2 Diabetes – both a risk and consequence of early stage Pan-Ca
Modifiable –Smoking active smoking remains the most established environmental modifiable risk factor for Pan-Ca Alcohol ( excessive ) Chronic pancreatitis Obesity and low physical activity Dietary factors ( some evidence that red and processed meat consumption is associated with Pan-Ca ) Infection H pylori hepatitis C Workplace exposure to certain chemicals eg chemicals used in dry cleaning and metal working industries
Presentation-Anatomical position- pancreas is located in the retroperitonium i.e the initial growth of the cancer is silent – symptoms indicate advanced disease. Where is the cancer located ? (see image ) rt upper quadrant or epigastric pain jaundice nausea or vomiting ( gastric outlet obstruction ) diarrhoea / stetorrhoea ( pancreatic insufficiency ) New or worsening back pain may indicate a location in body/tail. New onset diabetes or deterioration in previously stable diabetes ( uncommon ) Rapid and drastic weight loss Anorexia Thromboembolic disease
Pancreatic cancer action ( www.pancreaticcanceraction.org ) has produced a diagnostic guide for GPs – When to suspect pancreatic cancer- treatment resistant dyspepsia -Indigestion symptoms which are not responding to PPIs. Painless obstructive jaundice -Yellowing of the skin and whites of the eyes Pruritus Dark urine. New onset type 2 diabetes -Underweight Normal weight When there is no other associated metabolic condition or family history of diabetes. Altered bowel movements-Increased frequency Offensive smelling stools Steatorrhoea ( pale stools ). Back and or epigastric pain or discomfort-Radiating dorsally Relieved by sitting & leaning forward The back pain is often described as where the bra strap would fit. Unexplained weight loss vomiting or anorexia -Possible signs of malignancy Unexplained weight loss is a red flag Can occur without any pain or apparent change in digestion
NICE guidance on pancreatic cancer -Age 40 and over and have jaundice-Refer USC ( for an appt within 2 weeks ) for pancreatic cancer. Age 60 and over with weight loss and any of the following-diarrhoea back pain abdominal pain nausea vomiting constipation new onset diabetes-Consider an urgent direct access CT scan ( to be performed within 2 weeks ) or an urgent ultrasound scan if CT is not available , to assess for pancreatic cancer
Blood tests-Blood tests to consider FBC LFTs Prothrombin time CA-19-9 biomarker ○ lacks sufficient sensitivity or specificity to be useful for early pancreatic cancer diagnosis ○ useful to monitor disease progression , recurrence and/ or therapy response ( approved by FDA ) Biomarkers for early detection- an area of intense ongoing study/ research. Imaging-Imaging / Biopsy Multidetector CT ( MDCT ) revels excellent resolution of pancreas and surrounding vasculature ( most widely available best validated tool ) Can also be used to detect spread Dynamic-phase helical or spiral CT ( based on protocol ) Ultrasound- often used as an initial test with sensitivity and specificity of 90 % and 95 % May miss masses < 3 cm BMJ quotes that US can detect tumours > 2 cm with sensitivity of 80-95 % A NORMAL ULTRASOUND DOES NOT RULE OUT PANCREATIC CANCER Endoscopic ultrasonography ( highly sensitive ) with fine-needle aspiration biopsy done for most patients MRI – option for patients who cannot tolerate contrast PET , MRCP , ERCP – based on expertise , availability.
Differential –Chronic pancreatitis Bile duct stones Cancer in adjacent organs as • ampulla of vater • duodenal cancer • CBD Autoimmune pancreatitis Distant metastasis – to the retriperitoneal space behind and in the head of the pancreas Lymphoma in pancreas ( rare )
Treatment –Surgical resection is the only curative treatment for Pan-Ca- these patients have 5 yr survival rate of upto 22 % Pan-Ca – classified as ◘ resectible 10-20 % ◘ borderline resectible 30-40 % ( BRPC ) ◘ locally advanced / unresectable pancreatic cancer ( LAPC ) and ◘ advanced disease 50-60 % Chemotherapy in adjuvant setting is known to improve survival rates and is recommended for all Chemo-radiotherapy in neoadjuvant setting may also improve survival but needs further work Previously surgical resection of pancreas was associated with unacceptable levels of morbidity and mortality- this has improved now and pancreatic surgery can be performed safely with acceptable mortality rates of < 5 %
Complications- delayed gastric emptying –Failure of dietary progression after 7 days , prolonged use of NG decompression or emesis upon removal requiring reinsertion. pancreatic leak-Leak containing amylase occur within 1-2 wks of surgery and presents with abdo pain , fever High mortality and- managed by IV antibiotics / percutaneous drainage.Diabetes Pancreatic insufficiency ( bloating , diarrhoea , steatorrhoea )
References Pancreatic cancer : A review of clinical diagnosis , epidemiology , treatment and outcomes Andrew McGuigan et al World Journal of Gastroenterology November 21, 2018 Volume 24 Issue 43 Pancreatic cancer Jorg Kleef et al Nature Reviews Disease Primers Volume 2 2016 Pancreatic Cancer UK -Some key facts www.pancreaticcancer.org Epidemiology of Pancreatic Cancer ; Global Trends , Etiology and Risk Factors Prasantha Rawla et al World J Oncol .2019 Feb ; 10(1) : 10-27 Diagnosis and management of pancreatic cancer Zaheer S Kanji MD et al CMAJ , October 1, 2013 , 185 (14 ) NICE guideline NG 12 Suspected cancer : recognition and referral June 2015 BMJ Best practice Pancreatic cancer Challenges in diagnosis of pancreatic cancer Lulu Zhang et al World J Gastroenterol. May 21, 2018 :24 ( 19 ) : 2047-2060 Oncolex – Differential diagnoses of pancreatic cancer www.oncolex.org Pancreatic Cancer Action www.pancreaticcanceraction.org