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
