gastro Flashcards
HNPCC (Lynch)
- 4% of CRC
- microsatellite instability
- defect in one of the DNA mismatch repair genes (germline)
- A. dom
- most common extra-intestinal –> endometrial
FAP
<1% of CRC
-A. dom
ischaemic colitis area
watershed area - prone to hypo perfusion and ischaemia
-rectosigmoid junction / splenic flexure
dysphagia
malignant:
- shorter duration
- solid > liquids
- constant & progressive
- older
- ALARM SYMPTOMS
Benign:
- long hx
- both liquid and solids
- intermittent/unpredictable
- younger
- may have alarm symptom (e.g. wt loss in late course)
e. g. eosinophilic oesophagitis/ achalasia/ dysmotility/ benign stricture/ globus hystericus
Barretts
precursor of adenocarcinoma
-if low grade dysplasia on 2 occasions, 6 mth apart –> endoscopic ablation therapy or close surveillance
-LGD - annual risk progression to adenoca = 1.8%
-HGD - annual progression risk to adenoma = 10%
most effective rx for HGD - combi endoscopic resection & radio frequency ablation (RFA)
-oesophageal endoscopic mucosal resection (EMR) - HGD/Intramucosal carcinoma
barretts surveillance
recc, but min evidence
1. no dysplasia
< 3cm, no intestinal metaplasia - repeat, more bx -> if still no dysplasia, dc
< 3cm, with intestinal metaplasia - repeat OGD q 3-5 yrs
>3cm - repeat OGD q2-3 yrs
- indefinite
- PPI, repeat OGD in 6 mths - LGD
- repeat OGD in 6 mths –> if still LGD –> RFA or close surveillance (6 mthly OGD) - HGD or T1a adenoca (within mucosa/submucosa)
-MDT discussion
-RFA
-3 mthly f/up for 1 yr, then annually
type 1 b adenoca –> esophagectomy and lymphadenectomy
ascitic fluid analysis
SBP
- WCC >500
- neutrophil >250
Perf if 2/3
- total protein >10
- glucose < 2.8
- LDH > upper limit of normal for serum LDH
SBP
most common - E.coli, Klebsiella
- early abx
- discontinue non-selective b-blocker ( ~60% increase in mortality & higher risk of hepatorenal syndrome)
hepatorenal syndrome definition
- progressive rise in creat >150
- notmal urine sediment. No proteinuria
- absence of shock
- urine Na <10
- cirrhosis with ascites
- no response to 2 days of volume expansion & withdrawal of diuretics
- no nephrotoxic drugs
Hepatorenal syndrome
Type 1
- 2x increase in creat > 250 within 2 wks
- med survival - few wks
type 2
- diuretic resistant ascites
- slow increase in Cr > 150
- med survival - 6 mths
King’s college criteria for liver transplant
Acetaminophen induced
- arterial pH < 7.3 OR
- grade 3/4 encephalopathy with PT > 100 & Cr > 340
Non-acetaminophen induced
-PT > 100 OR
Any 3 of:
- age < 10 or > 40
- non-A & non-B viral hepatitis, idiosyncratic drug reaction, Wilsons
- Jaundice > 7 days
- PT > 50 secs
- bili > 180
Etoh hepatitis
spectrum: fatty liver -> etoh hepatitis > cirrhosis > HCC
Hx; CAGE
ALT/AST >2
Mod leucocytosis (<20,000)
Rx;
R/out -Hep A/B/C, biliary obst, Budd-Chiari
discrimination factor >32 –> high short term mortality –> steroids/pentoxifylline
MELD > 11 - high mortality
discontinue non-selective b-blocker TNF inhibitor (pentoxifylline) prednisone for 1 mth -> taper
AI Hepatitis
type 1
- SMA, ANA
- AMA, pANCA (helpful if all ab -ve)
- anti-actin ab
- spec 99% / sens 43%
type 2
- anti-LKM
- spec 99%
Mx;
-not req in asymptomatic/min transaminases, gamaglobulin, necroinflammatory
monoRx -pred indefinitely
combi - pred + AZA
wernicke’s encephalopathy
classic triad in 10%
- ophthalmoplegia (nystagmus)
- ataxia
- confusion
hep c genotype 3
Sofosbuvir + daclatasvir for 12 or 24 weeks or
Sofosbuvir + ribavirin for 24 weeks or
The combination of sofosbuvir + pegIFN + ribavirin for 12 weeks
barretts surveillance
No dysplasia: 3–5 years
Low-grade dysplasia: 6–12 months
High-grade dysplasia in the absence of eradication therapy: 3 months.
GLP-1
NAFLD
LEAN study - In summary, the study concluded that Liraglutide was safe, well tolerated, and led to histological resolution of non-alcoholic steatohepatitis, warranting extensive, longer-term studies.
inactive hepatitis B surface antigen (HBsAg) CARRIER state.
– HBsAg and HBcAb are positive. – normal liver enzymes (AST and ALT) – HBeAg and HBV DNA are negative – HBeAb is positive – asymptomatic
chronic hepatitis B, which is divided into
- HBeAg positive and
- HBeAg negative
HBeAg positive:
– HBsAg positive.
– HBV DNA positive
– liver enzymes are persistently or intermittently elevated
HBeAg negative(Precore mutant):
– HBsAg positive.
– HBV DNA positive
– liver enzymes are persistently or intermittently elevated
resolved chronic hepatitis B (Past infection)
– HBsAg negative
– HBsAb positive
– normalization of ALT and AST
– very low levels of HBV DNA(less than 10,000 copies/ml)
Hep b lab test
- surface antigen (HBsAg) is the first marker to appear and causes the production of anti-HBs
- HBsAg normally implies acute disease (present for 1-6 months)
- if HBsAg is present for > 6 months then this implies chronic disease (i.e. Infective)
- Anti-HBs implies immunity (either exposure or immunisation). It is negative in chronic disease
- Anti-HBc implies previous (or current) infection. IgM anti-HBc appears during acute or recent hepatitis B infection and is present for about 6 months
- HbeAg results from breakdown of core antigen from infected liver cells as is therefore a marker of infectivity
hep b status and lab
- acute Hepatitis B: High titres of IgM anti-HBc.
- chronic Hepatitis B: HbsAg positive, DNA positive, High titres of IgG anti-Hbc.
- Past infection (Not a carrier): HBsAg negative, HbsAb positive, HBeAb positive, core IgG positive, undetectable DNA
- Inactive carrier: HBsAg positive, HBeAb positive, HBcAb positive
- previous immunisation: HBsAb positive, ALL others negative
- Precore mutant: HbeAg negative, HBV DNA positive.
H. pylori initial Rx
PPI + clarithromycin + amoxycillin for 10-14 days
H.pylori failed ppi rx
Bismuth-based quadruple therapy: PPI + Bismuth + Tetracycline + Metronidazole for 10-14 days.
Sequential therapy: PPI + Amoxycillin for 5 days, followed by PPI + Clarithromycin + Tinidazole for 5 days.
Susceptibility driven therapy.
Salvage therapy: Levofloxacin (either triple or sequential) or Rifabutin triple therapy.
multitarget Stool DNA testing
- KRAS
- NDRG4
- BMP3
- β-actin, plus
- hemoglobin immunoassay.
leptin
from adipose
Functions:
1) Inhibits food intake by reducing the expression of neurotransmitters that increase food intake ie: Neuropeptide Y and agouti-related peptide.
2) Increases energy expenditure.
Indications for liver transplant
Chronic noncholestatic liver disorders:
- Chronic hepatitis C
- Chronic hepatitis B
- Autoimmune hepatitis
- Alcoholic liver disease
Cholestatic liver disorders:
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Biliary atresia
- Alagille syndrome
- Nonsyndromic paucity of the intrahepatic bile ducts
- Cystic fibrosis
- Progressive familial intrahepatic cholestasis
Metabolic disorders causing cirrhosis:
- Alpha-1-antitrypsin deficiency
- Wilson disease
- Nonalcoholic steatohepatitis and cryptogenic cirrhosis
- Hereditary hemochromatosis
- Tyrosinemia
- Glycogen storage disease type IV
- Neonatal hemochromatosis
Metabolic disorders causing severe extrahepatic morbidity:
- Amyloidosis
- Hyperoxaluria
- Urea cycle defects
- Disorders of branch chain amino acids
Primary malignancies of the liver:
- Hepatocellular carcinoma
- Hepatoblastoma
- Fibrolamellar hepatocellular carcinoma
- Hemangioendothelioma
Fulminant hepatic failure
Miscellaneous conditions:
- Budd-Chiari syndrome
- Metastatic neuroendocrine tumors
- Polycystic disease
Retransplantation
Specific recommendations on liver transplant
Hepatocellular carcinoma
– single lesion between 2 to 5 cm or
– no more than three lesions, the largest of which is less than 3 cm, and no radiographic evidence of extrahepatic disease.
– Liver transplantation should be viewed as the treatment of choice for selected patients with hepatocellular carcinoma who are not candidates for surgical resection and in whom malignancy is confined to the liver
Cirrhosis:
– referred for transplantation when they develop evidence of hepatic dysfunction (Child Pugh Score > 7 and MELD > 10) or when they experience their first major complication (ascites, variceal bleeding, or hepatic encephalopathy).
Hepatorenal syndrome:
– Patients with type I hepatorenal syndrome should have an expedited referral for liver transplantation
Morbid obesity (BMI >40 kg/m2) is a contraindication to liver transplantation
Alcoholic liver disease
– delay transplantation for a minimum of 3 to 6 months of abstinence from alcohol
Screening prior to liver transplant
1) Dobutamine stress ECHO if chronic smokers, age >50, clinical or family history of heart disease or diabetes.
Positive test confirmed with cardiac catheterization
2) Doppler ECHO for pulmonary hypertension- done to ALL patients.
3) Screen for osteoporosis in ALL patients
prognosis indicators for alcoholic hepatitis
Prognosis could be calculated based on the Child-Pugh score and MELD score.
The MELD score is based on objective measures (serum bilirubin, creatinine, and PTT) and the Child-Pugh class is based on both objective and subjective measures (serum albumin, PT, serum bilirubin, degree of ascites, and encephalopathy).