HPB Flashcards
Risk factors for pancreatic cancer
Non-modifiable:
Family history
Familial conditions - BRCA1, Lynch, FAP, Li-FRaumeni, Peutz-Jeghers, MEN, Von Hippel-Lindau, Fanconi, Gardener
Modifiable:
Smoking
Alcohol
DM
Gallstones or cholecystectomy
Chronic pancreatitis
Occupational exposure (asbestos, drycleaners, paint/varnish/textile industries)
Processed meat
Pathophysiology of pancreatic cancer
Arises from 3 different types of precursor lesions:
- Pancreatic intraepithelial neoplasia (most common)
- IPMN
- MCN
For PanIN, involves a stepwise progression from pre-neoplastic condition to invasive carcinoma involving a number of mutations
Normal
PanIN-1 (K-ras mutation 99%)
PanIN-2 (CDKN2a mutation 90%)
PanIN-3 (TP53 mutation 85% or SMAD4 mutation 55%)
Pancreatic ductal adenocarcinoma
Courvoisier’s sign
Palpable gallbladder with painless jaundice (present in < 25% of people with pancreatic Ca
Un-Resectability of pancreatic neoplasm
Borderline resectable
- Involvement of SMA or CHA (>180 degrees contact)
- Involvement of coeliac trunk or aorta
- Involvement of 1st jejunal branch of SMV or non-reconstructable PV or SMV
- Involvement of lymph nodes outside of resection margin
- Distant metastatic disease
Borderline
- Involvement of CHA or SMA <180 degrees
- Reconstructable involvement of PV or IMV
- Involved lymph nodes withint he field of surgery
Cystic pancreatic neoplasms
Neoplastic Mucinous
- IPMN side or main branch. Occur in 40-60’s, M=F. Mostly in HOP. High CEA and mucin on aspiration. 70% risk of malignancy in MB - for resection. 30% malignancy in SB - act as per fukuoka guidelines.
- MCN. F»M. 40-50’s (mother). Mostly in body and tail. Can be unilocular or septated. Kras mutations, moderate high CEA 200 and Mucin present on aspiration. Moderate malignancy risk . Resection recommended.
Neoplastic non-mucinous
- cystadenoma occurs in 40-60’s (grandma) and F»M. Located throughout pancreas and have honeycomb appearance on imaging with a starburst central scar due to calcificaitons in 20%. Low CEA on aspiration and high glucose. Columnar epithelium with glycogen in 50%. Low risk of malignancy so only resect if symptomatic.
- Solid pseudopapillary neoplasm occurs in young teens-30’s (daughter) and F»M. Can be very large (8cm), appear solid on imaging and mostly in the body and tail. Aspiration shows low CEA and cells with branching papilae and myxoid stroma. Beta catenin mutations present. Moderate malignant potential so should be resected.
Non neoplastic cysts
- Inflammatory cysts (acute peripancreatic collections, pseudocysts, acute necrotic collections, mature encapsulated necrosis
- Benign epithelial cysts
Retention cysts
Fukuoka guidelines
Determine risk of side branch IPMN
High risk features on imaging recommend resection
- obstructive jaundice
- Solid component > 5mm
- Main PD > 10mm
Worrisome features recommend EUS (not FNA)
- Pancreatitis
- Cysts > 30mm size
- Enhancing walls
- Enhancing nodule <5mm
- Main PD 5-9mm
- Raised CA 19-9
- Abrupt change in PD with distal atrophy
- Growth of cyst >5mm/ year
- Lymphadenopathy
EUS high risk features so recommend resection
- Definate mural nodules with doppler flow >5mm
- Main duct looks to have involvement (thick wall, mucin, nodules)
- Cytology susupicious for or confirms malignancy
Pathogenesis of acute pancreatitis
2 phases
- Acute inflammation
- Autodigestion
Inciting event combined with reflux or obstruction leads to initiation of pancreatitis characterised by acute inflammation
Local inflammation causes chemotaxis and activation of neutrophils and monocytes which release further cytokines such as IL1, IL6 and TNFa.
Proinflam response outbalances antiinflammatory response which leads to SIRS and further systemic complications (eg MODS)
Abnormal activation of proteolytic enzymes leads to colocalisation of lysozymes and zymgoen granules which allows activation of trypsinogen by cathepsin B. This causes acinar cell injury and allows further trypsin release, facilitating the zymogenic cascade.
The natureal pancreatic trypsin inhibitor is overwhelmed leading to erosion of vessels, hypoperfusion and necrosis
Risk factors for Gallstones
Female (estrogen causes increased chol content in bile)
Prev pregnancy
Family hx of GS
Rapid weight loss in morbidly obese patients
TPN use (causes GB hypomotility and increased lipid levels)
Fibrates (
Diet high in fat and carbs
T2DM
Sedentary lifestyle
Chrons (decreased reabsorption of bile acids)
Pathophys of gallstones
Cholesterol stones (90%)
- Supersaturation of one of the bile minerals or cholesterol causing crystallisation
- Mucin from the gallbladder acts as a nidus for crystal formation
- hypomotility of the gallbladder allows for preciitation of salts
Pigment stones (10%):
- Formed from excess of unconjugated bile from RBC breakdown.
Causes of portal hypertension
Pre-hepatic
- Portal, splenic or mesenteric vein thrombosis or compression
- Increased splenic flow (eg myelofibrosis)
Intra-hepatic -presinudoisal
- Sarcoidosis
- Schistomiasis
Intra-hepatic - sinusoidal
- Cirrhosis 90% of PH. Hepatitis, alcohol, PBC, PSC, hemochromotosis, Wilsons.
- Acute alcoholic hepatitis
- Cytotoxic drugs (oxaloplatin, stem cell Transplant meds)
Intrahepatic - post-sinusoidal
- Veno occlusive disease
Post-hepatic
- Budd-Chiari syndrome (thrombosis of hepatic veins)
- R heart failure
- Caval web
Bile duct injury
Strasberg-Soper
A - Leak from cystic duct or minor hepatic duct draining cystic plate
B - Occlusion of part of biliary tree (most commonly right hepatic duct
C - Transection without occlusion of right duct
D - Incomplete injury to CBD
E - further categorised by Bismuth classification
E1 - CBD injury > 2cm from cofluence
E2 - CBD injury < 2cm from confluenece
E3 - Injury to confluence without destruction
E4 - Complete destruction of confulence
E5 - R duct injury plus CBD stricture
Child Pugh score
Scoring system to describe the severity of liver dysfunction, and perioperative mortality.
Uses a number of 3 biochemical and 2 clinical criteria (bili, Alb, INR, ascites, encephalopathy)
- A: 1 yr survival 100%, periop mortality 10%
- B: 1 yr survival 80%, periop mortality 30%
- C: 1 yr survival 45%, periop mortality 82%
Causes of splenomegaly
Congestive (cirrhosis and portal HTN, CHF, PV or splenic thrombosis)
Malignancy (lymphoma, mets leukaemia)
Infection (EBV, CMV, TB, malaria)
Inflammation (RA - Felty syndrome, sarcoid, SLE)
Infiltrative (amyloid)
Hematological (Sickle cell, hemolytic anaemia)
Indications for splenectomy
Trauma
Haematological
- ITP
- Hereditary shperocytosis
-Sickle cell
- Autoimmune hemolytic anaemia
Malignancy
- Splenic mets (breast, lung, melanoma, colorectal, ovarian)
- NHL, CLL, CML
Infection
- Hydatid
Causes of chronic pancreatitis
Toxins (ETOH, Ca, lipids)
Idiopathic
Genetic (SPINK1, PRSS1)
Autoimmune
Recurrent panc
Obstruction - divisum, duct stricture, stone
PAthophysiology of chronic pancreatitis
Acute pancreatitis
- Inflammation
- Autodigestion
Chronic
- Profibrogenic cytokines lead to proliferation of myofibroblasts
- Production of collagen and ECM remodelling
- fibrosis of duct, dilatation of duct
- atrophy of acinar cells and wasting of gland
Acute Pancreatitis scoring systems
Glascow imrie (>3 is severe). Do at admission and 48 hours
PaO2 low
Age >55
Neutrophils / WBC >15
Calcium <2
Renal (urea > 16)
Enzymes (LDH >600)
Albumin < 32
Sugar (BSL>10)
Atlanta
Mild : No organ failure or complicaitons
Moderate: Organ dysfunction < 48 hours
severe: Persistent organ dysfunction > 48 horus
Pathology features of HCC
I don’t smack my caboose very much
- I nvasion of PV poor prognosis. Portal HTN
- D ifferentiation (Edmondson grade 1-4). Well, Moderate, poorly, un-differentiated
- S tains. GPC3, HSP70
- M utations. TERT promotor mutations in 60%.
C apsule: Can surround nodules, which can be invaded by tumour cells. Capsule has delayed enhancement
V ascularisation. Loss of portal suply and developoment of hepatic artery neovascularisation
M etastases. Commonly to lung, adrenals, bones, LN, meninges, pancreas, brain, kidney. Risk factors are large tumour size, poor differentiation and bilobar disease.
Staging and management of HCC
BCLC (barcelona clinic liver cancer)
0 - very early Stage
Single lesion < 2cm
Child-Pugh A
Good functional status
Tx: Resection, transplant, ablation
A - Initial Stage
Single lesion 2-5cm, up to 3 lesions <3cm
Childs-Pugh A
Good functional status
Tx: Resection, transplant, ablation
B - intermediate Stage
Multiple lesions
No invasion or spread
Childs-Pugh A or B
Non-cureative
Tx: TACE
C - Advanced Stage
Multiple lesions or invasion or mets
Childs-Pugh A or B
Impaired functional status
Non-cureative
Tx: Sorafenib
D - terminal stage
Any lesions if poor functional status, mets or advanced liver disease
Tx: Best supportive cares
Gallbladder cancer surgery - contraindications and options
Contraindications
- Distant disease (peritoneal, liver mets)
- Involvement of biliary tree or vasculature that precludes resection
- Involvement of distant nodes (coeliac, SMA, peripancreatic or duodenal)
Surgical options
- T1 (mucosa or muscle): cholecystectomy
- T2: Extended cholecystecotmy taking 4b and 5, with 2cm margins, plus portal LN dissection (portal, heptoduodenal ligament, retroduodenal
- T3-T4: Extended liver resection (may need right hepatectomy to clear)
