Pancreatic carcinoma Flashcards
(20 cards)
Epidemiology of pancreatic adenocarcinoma
- Overall prognosis: Poor due to late diagnosis. Lowest 5-year survival rate
- Only 10-20% eligible for resection
- 5 yr survival 7-25%
- Median survival
- Resectable : 1- 2 yrs
- Unresectable locally advanced (stage III) : 1 yr
- Metastatic disease : 2 – 6 months
Risk Factors for pancreatic carcinoma
Non-modifiable risk factors:
🎈Age – affect elderly with 90% of newly diagnose cases aged >55 years old
🎈Gender – male affected more than female
🎈Ethnicity – highest seen in African American population and Caucasian. Lowest in Asian population
🎈Blood group – Non-O blood group affected more. OR according to blood type B (1.7), AB (1.5), A (1.3)
🎈Family history – Familial cancer in 5-10%. Increase risk if positive 1st degree relative with pancreatic CA
🎈Diabetes mellitus – almost 2 -fold increase risk in patient with DM type 1 and 2
Modifiable risk factors:
🎈Smoking – OR for active smoker (2.0) and ex-smoker (1.2). Risk remains at least 10 years after stop smoking
and studies show it takes 20 years for risk to return to baseline
🎈Alcohol – increase risk with consumption >30g of alcohol per day
🎈Chronic pancreatitis – 5% of CP developed cancer. 13-fold increase compared to general population
🎈Obesity – increment 10% risk with every 5 BMI units above normal
🎈Infection – H. pylori and Hepatitis C infection found to have increased risk for pancreatic cancer
Familial association of pancreatic carcinoma
- Familial atypical multiple mole melanoma syndrome
- HNPCC
- Peutz-Jeghers Syndrome
- BRCA
- FAP
Classification of Pancreatic neoplasm
Pathology of Pancreatic carcinoma
Pancreatic ductal adenocarcinoma (PDAC) account for 90% of all pancreatic cancer
- 60-70% arise from head of pancreas, 15% in the body and another 15% from tail of pancreas
- WHO classify PDAC into histological subtype and each of subtype carry different prognosis
- PDAC develop after stepwise mutation of normal mucosa to premalignant and ultimately invasive carcinoma
- The most common precursors to PDAC are pancreatic intraepithelial neoplasia (PanIN), IPMN and MCN
PanIN is a non-invasive microscopic lesion (<5mm) in the small pancreatic duct
* It is graded into 1-3 reflecting progressive neoplastic morphological changes
* Lifetime risk for PDAC is 1-2% in PanIN 1 and estimation progression 10-12 years from PanIN 3 to PDAC
IPMN is a well-known premalignant precursor to PDAC and classify as main duct, side branch or mixed IPMN
* Main Duct-IPMN has higher risk of developing PDAC compared to Side Branch-IPMN
MCN is more commonly found in female and associated with malignancy in 15% of resected specimen
Clinical presentation of pancreatic carcinoma
- Majority are asymptomatic or presented with non-specific symptoms depending on location of the tumor
Commonest clinical presentations are:
- abdominal pain (40-60%)
- abnormal liver test (50%)
- jaundice (30%)
- new onset diabetes (10-20%)
- dyspeptic symptoms (20%)
- back pain (10%)
- weight loss (10%)
Tumor at head or neck can present with painless jaundice due to biliary obstruction
Pancreatic body tumor can invade surrounding neurovascular bundle leading to back pain
Tumor at pancreatic tail usually grow with minimal symptoms and tend to be advanced at presentation
Late presentation:
- UGIB
- Neuropsychiatric disturbances
- Polyarthritis, painful skin nodules (panniculitis – autodigestion of s.c fat due to systemic spillage of pancreatic enzymes).
- Vomiting due to gastric outlet obstruction
- Paraneoplastic syndrome associated
- hypercalcemia
- non-infective “marantic” endocarditis
- Symptoms related to metastatic disease
Examination findings of pancreatic carcinoma patient
- Upper abdominal mass,
- Jaundice
- Hepatomegaly, Splenomegaly
- Courvoisier’s sign (25%) – painless jaundice with palpable gallbladder is not due to stone therefore presumes the cause to be an obstructing pancreatic or biliary neoplasm until proven otherwise.
- Lymph Node : Virchow node, Sister Mary Joseph’s nodule, Blumer’s shelf in per-rectal examination (tumor has metastasized to pouch of Douglas).
- Ascites, peripheral oedema
- Paraneoplastic syndrome associated
- hypercalcemia
- acanthosis nigricans– skin fold hyperpigmentation
- thrombophlebitis migrans(Trousseau’s sign), 10% – recurrent, migratory superficial venous thrombophlebitis
- non-infective “marantic” endocarditis
- neuromuscular syndromes– dermatomyositis, polymyositis, Lambert-Eaton myasthenic syndrome
Principle of management in Pancreatic carcinoma
- Confirm diagnosis ( Tissue diagnosis is not necessary in resectable cases)
- Staging
- Operability
- Resectability
Investigation for Pancreatic carcinoma
Blood investigation:
- Basic blood
- Serum CA 19-9 has good sensitivity (80%) and specificity (90%) for pancreatic cancer
* It mainly uses for diagnosis, prognosis and evaluate response and surveillance
* Limiting factor of CA 19-9 is that it can also raise in benign condition and in case of biliary obstruction
- Patients not harboring a functional Lewis enzyme (Lea-b- genotype: 7%–10%
of the population), levels of CA 19-9 are typically undetectable or below 1.0 U/ml.
- Preoperative serum CA 19-9 level ≥500 UI/ml clearly indicates a worse prognosis after surgery.
Imaging:
1) USG Abdomen
- 1st line in obstructive jaundice to look for likely site of obstruction to decide on type of CT to order.
2) Contrast Enhanced CT Scan
- Pancreatic Protocol 3 phase, 1-3 mm cut, water as oral contrast: 74-98% accurate, 77-97% sensitive, 85-100% specific
- Plain - for calcifications within pancreas, which may indicate the presence of a focal pancreatitis.
- Early-portal phase (also Late arterial or the Pancreatic phase) - most important phase for detecting and staging a pancreatic tumor.
- Normal pancreatic parenchyma will enhance optimally, because it gets all of its blood supply through arterial and capillary system.
- There is optimal attenuation difference between hypodense tumor and normal enhancing pancreatic parenchyma.
- This phase helps in the differentiation of liver lesions and well opacified mesenteric arteries and veins.
- Late portal (hepatic phase) - performed for the overall assessment of the abdomen to look for liver metastases, lymph nodes and peritoneal implants.
- Also helpful for local staging of the tumor and detection of venous ingrowth.
- Hypo vascular tumor best seen on late arterial phase. Enhance poorly compared to adjacent normal pancreatic tissue and thus appear hypodense on arterial phase scans in 75-90% of cases, but may become iso dense on delayed scans (thus the need for multiple phase scanning when pancreatic cancer is the clinical question). Double duct sign (diagnostic of pancreatic head or periampullary C) may be seen.
3) MRI
- An alternative for detection of smaller lesions when CT is contraindicated
- Adjunct to CT in staging particularly for characterization of CT-indeterminate liver lesions
4) MRCP
- Provides information on the patency of biliary and pancreatic ducts
- Identifies vascular invasion
5) ERCP / PTC
- Allows diagnosis of periampullary tumors, image pancreatic duct (Brush cytology & HPE)
- Indication for preoperative biliary drainage
- No operating time for early surgery
- Cholangitis
- ERCP & SEMS is preferred method for PD
- Avoid liver puncture
- Allow brushing and biopsy for cytology & HPE
6) EUS
- EUS act as adjunct to assess LN involvement and relations between tumor and surrounding vascular structure
* EUS biopsy is safe and provide high yield for confirmatory tissue diagnosis ( 95%)
- Fear of tumor cell dissemination along needle track is a risk.
Percutaneous biopsy of a liver metastasis can be used in metastatic disease, but percutaneous biopsy of pancreas is contra-indicated in potentially resectable cases.
Operability assessment for Pancreatic carcinoma
1) Performance Status:
A score that estimates the patient’s ability to perform certain activities of daily living (ADLs) without the help of others.
- ECOG, ECG, CXR, Lung function test, ECHO
2) Physiological Reserve
Cardiopulmonary Exercise Test (CPET) - a non-invasive method used to assess the performance of the heart and lungs at rest and during exercise.
- Exercise modalities - selection of modality and protocol are dependent upon the requesting physician, level of fitness and health, weight, age, and patient preference
- Bicycle ergometer
- Treadmill
Information analyzed
- Lung Function: Flow volume loops
- Oxygen Consumption during exercise (VO2 max)
- Anaerobic Threshold
- Heart performance during exercise
- Blood gas measurement from blood sample taken from the earlobe
- Exercise 12 lead ECG
ECG, CXR, ECHO, Lung function test
Nutritional status
- FBC : Anemia, TLC for nutritional status
- LFT : Albumin for nutrition.
- PT/PTT : Deranged due to ↓ Vit K absorption in obstructive jaundice.
- HbA1c : New onset DM
Criteria for Resectability of pancreatic ca.
Borderline resectable:
- abutment or encasement of hepatic artery if reconstructible
- less than 180 degree tumour abutment on SMA
- short segment occlusion of SMV if reconstructible
Overview of Pancreatic ca. treatment
Treatment for Resectable disease.
Head of pancreas tumor:
Pancreatoduodenectomy (Whipple’s)
- Dissection of right hemi-circumference of SMA to right of coeliac trunk is recommended to obtain a good medial clearance and to improve rate of R0 resection.
- Distal stomach resection reduces gastric emptying dysfunction and density of parietal cells (less risk of gastritis), but dumping syndrome, bile reflux and 10-20% risk of pancreatic fistula.
- Frozen sections analysis of pancreatic neck transection and common bile duct transection margins is recommended.
Pylorus-Preserving Pancreaticoduodenectomy (PPPD)
- No evidence that extended lymphadenectomy +/- portal vein resection is superior than standard lymphadenectomy
- Retains function of pylorus, good gastric function, reduces dumping and bile reflux, risk of recurrent cholelithiasis.
- Right gastric artery preserved and duodenum resected 2 cm distal to pylorus.
British Royal College of Pathologists (RCpath) specimen examination and R1 definition (margin <1 mm) advises surgeons to identify following margins:
- anterior, posterior, medial, or superior mesenteric groove, SMA, pancreatic transection,
bile duct, and enteric.
- Tumor clearance should be given for all seven margins
Lymphadenectomy
- Standard lymphadenectomy for pancreatoduodenectomy should resect the following lymph nodes: ≥15 lymph nodes should be removed to allow adequate pathologic staging
Treatment for Resectable disease. (2)
For body & tail of pancreas cancer
Distal pancreatectomy + Splenectomy + en bloc LN dissection
- Radical anterograde modular pancreatosplenectomy (RAMP), with dissection of left hemi-circumference of SMA, to the left of coeliac trunk, recommended to ensure R0 resection
Lymphadenectomy
- Standard lymphadenectomy for tumors of body and tail of pancreas should resect the following lymph nodes: ≥15 lymph nodes should be removed to allow adequate pathologic staging.
Total Pancreatectomy
- No role of total pancreatectomy unless it is the only way to achieve R0 resection
- Surgical mortality = 5%, morbidity 30%
- Reoperation rate ~10%; mortality for reoperation ~60%
Post operative complication
Complications
- Pancreatic fistulae
- Delayed gastric emptying
- Hemorrhages
- Wound infection
- Intra-abdominal sepsis
- Acute pancreatitis
- Portal vein thrombosis
- Chylous ascites
- Bile leaks
Treatment for Borderline resectable Pancreatic tumour
- Patients with borderline resectable lesions should be included in clinical trials wherever possible
- If not included in a trial, a period of chemotherapy (gemcitabine or FOLFIRINOX) followed
by chemoradiation and then surgery appears to be the best option. - Tumors are considered resectable upon good response to neoadjuvant treatment including induction chemotherapy, preoperative chemoradiation or a combination of both.
- Adjuvant therapy is considered standard after findings of landmark trial CONKO-001 (2010) which compare
adjuvant gemcitabine vs surgery alone. Increase median DFS, 5-years and 10-years survival with gemcitabine - ESPAC-4 (2017) trial shown median OS better in combination of capecitabine/gemcitabine vs gemcitabine alone
- PRODIGE-24 (2018) trial demonstrates better DFS and OS of another combination mFOLFIRINOX vs gemcitabine
* mFOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) is mainly used in very fit patients - For less fit patient (ECOG >1) dual therapy capecitabine and gemcitabine is mainly used
Treatment for Locally. Advanced Disease of pancreatic ca.
When patient has no metastases and tumor is not considered as borderline resectable, the tumor is defined as truly locally advanced.
- Regardless of the treatment strategy, average OS for these patients remains low (<1 year) in oldest studies.
- Standard of care is 6 months of gemcitabine.
- A minor role of chemoradiation in this subgroup of patients observed
- At least 1/3 of patients with PDAC presented at locally advanced stage with extensive vascular involvement
- The treatment in this group primarily systemic chemotherapy using established regime for metastatic disease
* Gemcitabine + nanoparticle albumin bound, nab-paclitaxel or FOLFIRINOX mainly used in this group - Surgery can be considered in patient with excellent response to chemotherapy, but majority remain incurable
Locally Advanced (Unresectable, Non-metastatic)
❌ Surgery not possible at diagnosis
Definition:
Tumor encases >180° of SMA/celiac axis
Unreconstructable involvement of SMV/portal vein
No distant metastasis
Management:
🧪 Definitive chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel)
🔄 Restaging for potential conversion to surgery (rare)
Treatment for Metastatic disease of pancreatic. ca.
Metastatic disease
* Considered incurable with current available therapy with poor prognosis. Medial survival <6 months
* Systemic chemotherapy can be considered in patients with good performance status
1) Disease Control
Chemotherapy:
- > 80% have unresectable tumors
- Ductal adenocarcinoma is resistant to conventional cytotoxic agents
- Patients with ECOG 2 due to heavy tumor load, gemcitabine and nab-paclitaxel can be considered for best chance of response.
- Patients with performance status of 2 and/or bilirubin level higher than 1.5× ULN: monotherapy with gemcitabine could be considered.
- Performance status of the patient is 0 or 1 and the bilirubin level is below 1.5× ULN two types of combination chemotherapy FOLFIRINOX regimen or combination of gemcitabine and nab-paclitaxel should be considered.
2) Symptom Control
Relieve Jaundice
- Biliary stenting: the endoscopic method is safer than percutaneous insertion and is as successful as surgical hepato-jejunostomy.
Relieve gastric outlet obstruction
- Gastrojejunostomy
- Expandable metal stent in duodenum
Pain management :
- WHO analgesic ladder
- In severe pain:
- Endoscopic pancreatic duct decompression
- Ablation of coeliac ganglia w 5% phenol or 50% ethanol (percutaneous, endoscopic US-guided, laparoscopic or open)
- Thoracoscopic division of splanchnic nerve
- Local radiation +/- chemo Rx may palliate pain
- Coeliac block
Other measures:
- Pancreatic enzyme supplements – if patient has features of malabsorption
- Omega-3 fatty acids (fish oil), thalidomide - may help reverse cachexia
Overview of treatment for Pancreatic ca.
causes of raised CA 19-9
⚠️ Malignant Causes
🔴 Pancreatic adenocarcinoma (most common use)
🔴 Cholangiocarcinoma (intrahepatic/perihilar/distal bile duct)
🔴 Gallbladder cancer
🔴 Hepatocellular carcinoma (occasionally)
🔴 Gastric cancer
🔴 Colorectal cancer
🔴 Ovarian mucinous tumors
🔴 Lung cancer (rarely)
⚠️ Benign Causes
🟠 Hepatobiliary Conditions:
- Obstructive jaundice (e.g., choledocholithiasis, biliary stricture)
- Acute or chronic cholangitis
- Primary sclerosing cholangitis (PSC)
- Cirrhosis
🟠 Pancreatic Conditions:
- Chronic pancreatitis
- Acute pancreatitis
- Pancreatic pseudocyst
🟠 Other Conditions:
- Cystic fibrosis (due to chronic inflammation)
- Inflammatory bowel disease (e.g., ulcerative colitis)
- Hypothyroidism (rarely)
- Interstitial lung disease (in rare reports)
