Module 2.4: Pancreato-biliary Flashcards
Types of Primary Pancreatobiliary Malignancy
• Pancreatic Adenocarcinoma
o Often involves head and neck and the acinar ducts obstruction develops when cancer develops around bile duct that runs through head of pancreas/due to lymph node swelling
o Those with cancer in the body or tail of pancreas are unlikely to present early as bile duct will not be affected no symptoms: jaundice/pale stools/dark urine
• Cholangiocarcinoma
o Cancer of the bile duct may cause obstruction
• Ampullary carcinoma
o Affects ampulla which is where common bile duct and pancreatic duct meet
o Radiologically: double duct sign: dilatation of both ducts is seen (bile duct and pancreatic duct)
• Gallbladder Carcinoma
o Can present with biliary obstruction
Causes of Secondary Pancreatobiliary Malignancy
o Breast
o Lung
o Lymphoma lymph node swelling can obstruct bile duct
o Melanoma
management of Malignant Bile Duct Obstruction
- 75-80% carcinoma head of pancreas.
- 15-20% considered for curative surgery.
• The majority managed by:
o Stenting
o Chemotherapy (not curative in pancreatic cancer)
Types of stent in bile duct obstruction
o Plastic stents
o Self-expanding metal stents (SEMs) allow for better drainage, less occlusion of stents and remodelling of ducts more, can come fully covered/uncovered use depends on whether patient is palliative as well as personal preference (uncovered = reduced migration rate, covered = if clogged up by tumour, there is less tumour ingrowth so it is easier to remove and insert a new one)
Describe the types of plastic stents used in bile duct obstruction and their limitation
• Two varieties o Pigtail: split the duct open o Straight: allows bile drainage out of the system within stent must ensure stricture is tight enough to secure this, if not use pigtail stent as it allows anchoring (see right) • Limitation: o High occlusion rate
Describe the use of SEMs in bile duct obstruction
- Flexible come compressed and are deployed once passed through endoscope working channel
- Tensile strength springs open and is able to remodel strictures
- Fully covered metal stents has an inner mesh that prevents it from embedding into the bile duct
• Advantages:
o Patency of SEMs is better than plastic stents
o Plastic stents becomes occluded more quickly à usually within 3 months compared to SEMs = 6 months
o If stents become occluded patients become really sick and septic this can interfere with chemotherapy regime
Endoscopic Management of Pancreatic Cancer
• Sewnath ME, Ann Surg 2003: Meta-analysis that looked at 5 trials with 302 patients and worked to determine whether pre-op drainage was useful prior to Whipple’s procedure
o Pre-op drainage caused:
Increased complications (ERCP carries its own risks e.g. pancreatitis)
No survival benefit
Prolonged hospital stay
How can malignancy of the bile duct be confirmed?
• Cross-sectional Imaging
o CT scan is good for mass lesions
o MRCP good for outlining biliary and pancreatic structures
• Tumour Markers – Ca19-9 (not specific, but helpful in the extremes e.g thousands, or single digits)
• Immune Markers
• Histology
• Cytology (tissue diagnosis of C5 indicates cancer)
• Cholangioscopy
Types of Benign Hilar Structures
• Covera et al 2005: study that showed that not all hilar strictures are malignant
o 22/275 (8%) of resections were confirmed as benign disease due to:
Lymphoplasmacytic sclerosing disease
Primary sclerosing cholangitis
Granulomatous disease
Non-specific fibrosis
Stone disease
Uses of Selective MRCP and CT Targeted Drainage
Hintze et al 2001, Freeman et al 2003:
o Aim to drain a minimum of 30% of biliary tree
o Optimally to place one stent to achieve drainage
o Two or more stents are placed if:
30% of liver drainage is not achievable
To drain all opacified segments
- Unilateral placement 85%, bilateral in 15%
- Low cholangitis rates
- Clinically successful bile drainage in 75%
- Always must choose to drain the area with the most functioning liver
Developments in Endoscopic Palliation
• Photodynamic Therapy
• Radiofrequency Ablation via Biliary Catheter
o Sets up heat rim around catheter and burns tumour at repeated points, balloon any necrotic tissue
o Done as often as is required
o Stents can be cleared up using this method
• Removable/Self Absorbing Stents
• Drug Eluting Stents
Stenting for Malignant Bile Duct Obstruction - Summarise
- Management dependant upon detailed pre intervention assessment.
- Metal stenting in almost all settings.
- Covered stents may be optimum in extrahepatic obstruction.
- Intervention for hilar strictures requires multi disciplinary approach.
- New techniques for improving stent patency /relieving stent occlusion
Define Endosonography
use of high frequency miniature ultrasound transducer incorporated into the tip of a conventional endoscope resulting in an enhanced resolution of the GI wall and strictures with close proximity to the GI wall.
Advantages and disadvantages of endosonography
• Advantages
o High intrinsic spatial resolution
o No ionizing radiation
o Inexpensive and easily portable
• Disadvantages
o Gas and bone impede the passage of USS waves, acoustic shadows can also be caused by calcification
o As good as the operator
o Only planar view taken
Types of Echoendoscopes
o Radial used for upper GI cancers
o Linear allows needles to be placed to take samples, most commonly used
o Miniprobes
Indications of endosonoscopy
o Staging of malignant GI tumours: ampulla of Vater, extrahepatic bile ducts and pancreas. (see how deep into the tissue the cancer goes)
Assessing the extent of ampullary adenomas/malignancies (adenoma seen on right)
o Obtain FNA/Biopsy of lesions in accessible organs including mediastinal lymph nodes
o Therapeutics: Perform coeliac plexus block – for pain relief; facilitate biliary and pancreatic access when ERCP fails
Complications of endosonography
o Perforation (1%) o Bleeding (<1%) o Sedation related cardiorespiratory problems o Pancreatitis (0.9%) o Infection (0.1%) must give antibiotics
• EUS in Pancreatic Cancer
o Post-operative 5 year survival for pancreatic Ca is 20 %
o Incomplete resection and positive nodes carry bad prognosis
o EUS may help to better select patients for curative surgery or to identify the non surgical candidates as it can be used to detect, stage, vascular invasion and resectability of pancreatic cancers. It is also better at defining lesions <2-3cm but more studies are needed to confirm this.
Describe the uses of the celiac nerve block
- Relatively easy and safe to perform (Alcohol and bupivicane used to ablate the plexus)
- Similar success rate to other methods but less invasive
- Diarrhoea main complication
- Useful in pancreatic Ca related pain but not in CP
Clinical Features of CC
• Rare before 40 years
• Presenting features depend on location
o Tumours at bifurcation of hepatic ducts or in distal CBD classically present with biliary obstruction:
Painless jaundice
Pale stools
Dark urine
Pruritus
o Peripheral tumours, arising within intrahepatic ducts of the liver parenchyma itself, present with non-specific symptoms:
Malaise
Weight loss
Abdominal pain
• Cholangitis is an unusual presentation
• Most patients have unresectable disease and die in less than 12 months due to:
o Liver failure
o Cancer cachexia
o Recurrent sepsis, secondary to biliary obstruction
Explain the poor prognosis in CC
- Overall 5-yr survival, including resected patients: <5 %
- This has not changed significantly over the past 30 years
- Possibly due to difficulty in confirming a diagnosis: (no classical imaging features, difficult area to reach with biopsy needle/unaccessible, no tumourmarker to aid diagnosis), patients present very late, risk factors only account for 20% of presentations
Classification of CC
• 90% are adenocarcinomas
• 50 – 60% are “Peri-Hilar”
arise at bifurcation of hepatic ducts (aka “Klatskin” tumours, usually classified as ICC) (pCCA)
- 20 - 30% in distal common bile duct (CBD)
- 10-20% are intrahepatic (iCCA)
- 5 - 10% are “peripheral”, arising within intrahepatic ducts of liver parenchyma itself
Classification of Biliary Structures
Bismuth
- Type I: Tumours below the confluence of L and R hepatic ducts
- Type II: Tumours reach confluence but not involving L or R hepatic ducts
- Type III: Tumours occlude the common hepatic duct and either right (IIIa) or left (IIIb) hepatic duct
- Type IV: Tumours that are multi-centric or involving both right and left hepatic ducts
Epidemiology of cc
o CC makes up 3% of all GI cancers
o 2nd commonest primary hepatic tumour
o Peak age: 7th decade
o Sex incidence: slight male preponderance
o Incidence rates for IHCC vary worldwide, reflecting local geographical risk factors and genetic differences in various populations
o Highest rates in NE Thailand (96/100,000 men), China and other parts of Southeast Asia
Possibly due to liver flukes (environmental exposure)
o Incidence in USA: 1-2 cases/100,000 (3,500 new cases/year); Australia 0.2/100,00 (men)
o Rising incidence rates, paralleled by mortality rates, documented worldwide
• Recent international studies of incidence + mortality rates show that:
o ICC increasing
o ECC decreasing
Explain the problems with the CC epidemiological data
Perihilar CC has been misclassified as intra or extrahepatic in different classification methods
ICD-0-1 - intra OR extra
ICD-O-2 - coded as INTRA (1991)
ICD-O-3 - coded as INTRA or EXTRA again
misclassified in all versions, esp 2
Note that pCCA is 50-60% of all CCA
Need International Consistency in Classification of CCA – to allow accurate monitoring of epidemiology
- ICD11 will resolve this
- Proposed:
o 2C18.0 Hilar Cholangiocarcinoma
o 2C12.10 Intrahepatic cholangiocarcinoma
o 2C15.0 Extrahepatic cholangiocarcinoma: Adenocarcinoma of biliary tract, distal bile duct
o Similar needed for ICD-O 4 i.e. three separate topography/morphology codes for iCCA, pCCA and dCCA
Aetiology and Risk Factors of CC
- Primary sclerosing cholangitis – biggest RF in the western world
- Parasitic Infection
- Fibropolycystic Liver Disease
- Intrahepatic Biliary Stones
- Chemical Carcinogen Exposure
- Viral Hepatitis
- Cirrhosis, Fatty Liver Disease/Metabolic Syndrome
Unlike with HCC where 90% of patients have cirrhosis, in CC this percentage is much lower (only a minority)
cirrhosis accounts for very few cases of CC.
Primary Sclerosing Cholangitis (PSC) in CC
• Commonest predisposing condition for CC in West
o Autoimmune disease that results in inflammation of bile ducts for many years
• CC rates of 8 - 40% reported in PSC pts in f/up studies and explant specimens
• CC in PSC presents earlier, in 30 - 50 year age groups
• 1/3 of PSC patients who develop CC do so within 2 years of PSC diagnosis
• Risk of CC unrelated to the duration of PSC
• 2/3 of PSC patients have IBD (UC): no association between CC risk and presence/severity of IBD
Parasitic Infection in CC
• Liver fluke infestation:
o Opisthorcis viverrini
o (Clonorchis sinensis)
• Case-control studies
• Syrian hamsters
• Most data from Thailand
o World’s highest CC rates: 96/100,000 population
o 7 million have opisthorciasis
• Humans infected by eating undercooked fish; adult worms inhabit and lay eggs in biliary tree
• CASCAP: Current strategy for screening is being implemented in those at risk from eating undercooked fish stool samples of patients to check for liver flukes, treat if they flukes present with praziquantel, check bile ducts with USS, if signs of stricturing these patients are sent to have a CT to check for CC
o Problem: people will eat raw fish again and become re-infected (vaccine may be better alternative, has not been developed)
Fibropolycystic Liver Disease in CC
• Congenital abnormalities of biliary tree associated with:
o Caroli’s syndrome
o Congenital hepatic fibrosis
o Choledochal cysts
• 15% risk of malignant change after 2nd decade (average 34y)
• Overall incidence of CC in pts with untreated cysts up to 28%
Intrahepatic Biliary Stones (Hepatolithiasis)
• Rare in West, relatively common in Asia
o Unsure why this happens
• Associated with peripheral ICC
• Up to 10% of patients with hepatolithiasis develop CC
• Taiwan: up to 70% of CC pts undergoing resection
• Japan: 6 – 18%
• Mechanism: biliary stones cause bile stasis recurrent bacterial infections/inflammation
Chemical Carcinogen Exposure in CC
• Promutagenic DNA adducts demonstrated in CC tissue
o Thorotrast: RR X 300 used to be a chemical contrast used in imaging (now banned due to association with CC) [iatrogenic cause]
• Associations with exposure to by-products from the rubber and chemical industries, including:
o Dioxins
o Nitrosamines (also produced by bacteria in fish, foods)
o Alcohol
o Smoking
• Results conflicting: no firm conclusions
Cirrhosis and Viral Hepatitis in CC
• Cirrhosis, of any cause, associated with CC
o 10% of all HCCs have mixed features of CC and HCC (known as mixed HCCs)
• Sorenson et al., Hepatology 1998: performed a cohort study on >11000 cirrhotic patients and followed them up for 6 years, found a 10-fold increased risk of CC compared with general population
• Shin et al., Int J Epidemiol 1996: case-control study performed in Korea found that 12.5% of CC cases were HCV+ and 14% HBsAg+ (compared to 3.5% and 2.3% of controls)
• Donato et al., Cancer Causes Control 2001: case-control study in Italy found that 23% of CC patients were HCV+ and 11.5% HBsAg+ (compared with 6% and 5.5% of controls)
• Kobayashi et al., Cancer 2000: performed a prospective control study in Japan and found that risk of CC in HCV-cirrhotic patients were 3.5% in 10 years
• HCV RNA has been detected in CC tissue
