GI - Gallstones, Pancreatitis, Cholangiocarcinoma, RPC, Liver abscess, Pancreatic cancer Flashcards
Gallstones /
- Types
- Risk factors
Types:
- Cholesterol - Cholesterol monohydrate
- Black pigment - calcium bilirubinate
- Brown pigment - Calcium bilirubinate, palmitate, sterate
- Mixed - Cholesterol + calcium salts
RF:
- Cholesterol: “4F”, Excessive cholesterol secretion and Gallbladder stasis
- Black pigment: Increase heme turnover/ hemolysis, Bile acid malabsorption, GB stasis
- Brown pigment: Bacterial infection of biliary tree
- Mixed: All of the above
Screening for risk factors of gallstone disease in history taking *
Female, Middle age
Obesity
Gallbladder stasis: Pregnancy or high estrogen state, Previous gastrectomy/ truncal vagotomy, low enteric intake/ Long-term parenteral nutrition
Liver cirrhosis
Hemolytic conditions
Diabetes mellitus: excessive cholesterol secretion
BM/ solid organ transplant
4 diseases stages of gallstone disease /
- Lithogenic state: risk factors cause Microlithiasis suspended in bile
- Asymptomatic GS: incidental finding on imaging
- Symptomatic GS: Biliary colic +/- fat intolerance, dyspepsia
- Complicated GS: Cholecystitis, CA gallbaldder, Cholangitis, Gallstone pancreatitis and ileus …etc
Brief investigation and workup plan for Gallstone disease *
P/E + blood tests: should be normal in uncomplicated GS disease
First-line: Trans-abdominal US: most sensitive modality for GB stones
- Stones: echogenic foci that casts an acoustic shadow
Second-line:
MRCP: usually as 2nd line if TAUS -ve
EUS ± bile collection: identify small stones missed on TAUS
CT scans: look for complications
ERCP/ PTBD: therapeutic intervention
Surgical treatment options of gallstone disease *
Laparoscopic cholecystectomy: Early or delayed LC
Gallbladder drainage:
Percutaneous transhepatic cholecystostomy
Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD)
Endoscopic transpapillary drainage by ERCP (ETGBD)
Combination of surgical treatment options for CBD stone + Gallstones *
Pre-operative ERCP + Cholecystectomy: Most common
Laparoscopic cholecystectomy + Exploration of CBD: Emergency
Laparoscopic cholecystectomy + on-table ERCP
Complications of gallstone disease *
Acute cholangitis, gallstone pancreatitis
Cholecystoenteric/ Choledoduodenal fistula + Gallstone ileus
Gangrenous cholecystitis - Sepsis
Emphysematous cholecystitis - secondary infection of the gallbladder wall with gas-forming organisms such as Clostridium perfringens
Gallbladder perforation: usually contained in the subhepatic space by the omentum, perforation into adjacent organs
Gallbladder Mucocele
Acute pancreatitis /
Mild, moderate and severe presentation
Mild
• Absence of organ failure and local or systemic complications
Moderately severe
• Transient organ failure resolving within 48 hours
• Local or systemic complications without persistent organ failure > 48 hours
Severe
• Persistent organ failure involving one or multiple organs
Scoring system for severity of acute pancreatitis *
Ranson’s criteria (11 criteria)
Most commonly utilized predictor of mortality associated with acute pancreatitis
GALL ETOH
Glucose, Age, Lymphocyte, LFT, Electrolytes, Third spacing BUN, Oxyghen, Hematocrit
o Score < 3: Mortality = 0 – 3% (Mild acute pancreatitis)
o Score ≥ 3: Mortality = 11 – 15%
o Score ≥ 6: Mortality = 40%
Causes of acute pancreatitis and pathophysiology of each cause (9)
Gallstone: Reflux of bile into pancreatic duct
Alcoholism: Increases synthesis of digestive and lysosomal enzymes by pancreatic acinar cells
Hypercalcemia: High PTH, Formation and deposition of calcified stones intraductally in pancreatic duct
Hypertriglyceridemia: Lipase is thought to liberate toxic fatty acids into the pancreatic microcirculation
Post-ERCP
Drug-induced: Steroids, Diuretics, Azathioprine, DDP-4 inhibitors, Valproate, Sulphonamides
Infections
Tumours: Pancreatic or periampullary tumors
Autoimmune diseases: SLE, Sjogren’s, PBC
Causative infective agents of acute pancreatitis *
Bacteria = Mycoplasma/ Legionella/ Leptospira
Virus = Mumps/ Coxsackievirus B/ HBV/ EBV/ CMV/ VZV/ HSV/ HIV
Fungi = Aspergillus
Parasites = Ascaris/ Clonorchis sinensis/ Toxoplasmosis/ Cryptosporidium
Describe the anatomical location of 4 sections of pancreas /
4 sections from right to left: Head/Uncinate Neck Body Tail
o Head of pancreas is cradled by the C-loop of duodenum
o Neck of pancreas lies anterior to the mesenteric vessels and portal vein
o Body of pancreas begins at the left border of SMV
o Tail of pancreas sits close to the splenic hilum anterior to left adrenal gland
Arterial and venous supply of pancreas /
Arterial supply: Celiac trunk/ Superior mesenteric artery (SMA)
Head of pancreas
Superior pancreaticoduodenal arteries (from GDA)
Inferior pancreaticoduodenal arteries (from SMA)
Tail of pancreas
Splenic artery branches
Venous drainage: Superior and inferior pancreaticoduodenal veins (into SMV) Splenic veins (into portal vein)
Complication of acute pancreatitis *
- *Pseudocyst**
- *Infected pseudocyst**
- *Necrotizing** pancreatitis
- *Hemorrhagic** pancreatitis
Pleural effusion
- *Ascites**
- *Splenic vein thrombosis**
Pathophysiology of acute pancreatitis /
Initial insult = Unregulated premature activation of pancreatic enzymes such as trypsin within pancreatic acinar cells
- Autodigestion of pancreatic tissues leading to peripancreatic and pancreatic necrosis
- Autodigestion extends beyond the pancreas into the retroperitoneum, causing fat necrosis and erosion of blood vessels with hemorrhage
- Entry of enzymes into the bloodstream may cause respiratory and renal injury
Systemic events
• NFᴋB-dependent inflammatory pathway
• Inflammatory cells lead to further acinar cell injury
Acute pancreatitis /
S/S
Fever
Abdominal pain
• Site: Epigastric pain but can be in RUQ or rarely LUQ
• Onset: Rapid onset (gallstones)/ Less abrupt (alcoholism)
• Character: Severe
• Radiation: Radiates to the back
• Associated symptoms: Nausea and vomiting
• Time course: Persists for several hours to days
• Relieving factors: Sitting up or leaning forward
Dyspnea
• Diaphragmatic inflammation secondary to pancreatitis
• Pleural effusions
• Adult respiratory distress syndrome
Ddx acute pancreatitis /
Differential diagnosis
Peptic ulcer disease
Choledocholithiasis/ Cholangitis/ Cholecystitis
Hepatitis
Mesenteric ischemia
Intestinal obstruction
Myocardial infarction*
Diagnostic criteria of acute pancreatitis /
Diagnosis of acute pancreatitis required 2/3 of the following
• Acute onset of persistent, severe, epigastric pain often radiating to the back (Clinical)
• Elevation of serum amylase or lipase to ≥ 3x upper limit of normal (Biochemical)
• Characteristic findings of acute pancreatitis on imaging including transabdominal USG, contrast-enhanced CT and MRI (Radiological)
Typical signs on abd. exam for acute pancreatitis /
• Inspection
o Abdominal distension
o Pancreatic panniculitis: Tender red nodules frequently occur in distal extremities
o Intra-abdominal bleeding: Cullen’s sign, Grey Turner sign
• Palpation
o Epigastric tenderness
o Hepatosplenomegaly (alcoholic pancreatitis)
• Auscultation
o Hypoactive bowel sounds (inflammation)
Biochemical tests for acute pancreatitis /
CBC with differentials
• Leukocytosis
• ↑ Hematocrit
Serum inflammatory markers
• ↑ CRP levels
LFT
• ↑ Conjugated bilirubin
• ↑ AST, ALT and ALP
RFT
• ↑ Creatinine and blood urea nitrogen (BUN)
Serum BG level
• Hyperglycemia or hypoglycemia
Serum Ca2+ level
Serum and urine amylase level ≥ 3x upper limit of normal
Serum lipase level ≥ 3x upper limit of normal
Cardiac markers ± ECG
• Troponin (TnI, TnT) to exclude myocardial infarction (MI)
Radiological tests for acute pancreatitis *
Features suggesting acute pancreatitis on each test
USG abdomen
• Pancreas appears diffusely enlarged and hypoechoic on ultrasound
• Presence of gallstones in gallbladder or bile duct
• Peripancreatic fluid collection appears as anechoic collection
Abdominal X-ray
• Sentinel loop - Localized ileus
• Colon cutoff sign - functional spasm of descending colon
• Ground-glass appearance - acute peri-pancreatic fluid collection
CT abdomen with contrast: for complications like pancreatic necrosis, biliary obstruction…etc
First-line treatment of acute pancreatitis *
General:
- IV fluid resuscitation
- O2 supplementation
- Enteral* nutritional support with electrolyte and glucose correction
- Foley catheter
- NPO with NG tube suction
Medical:
- *Analgesic: NSAID** (Not opioids to avoid sphincter of Oddi spasm)
- *Antibiotics** for pancreatic necrosis >30% : Imipenem* or meropenem; carbapenems, fluoroquinolones and metronidazole
First-line Surgical treatment options for acute pancreatitis *
Surgical options for complications
Endoscopic retrograde cholangiopancreatography (ERCP)
Percutaneous transhepatic biliary drainage (PTBD)
Exploration of common bile duct (ECBD)
-
Necrosectomy:
o Open = Laparotomy/ Retroperitoneal approach
o Minimally-invasive = Endoscopic or percutaneous radiologic
Complications:
- Pancreatic pseudocyst and walled-off necrosis >> surgical drainage by endoscopy, percutaneous catheter or surgical debridement
- Infected necrosis; antibiotics + percutaneous catheter drainage or endoscopic drainage
- Pseudoanerysm - ABSOLUTE contraindication to endoscopic drainage
Cholangiocarcinoma *
- Definition
- Histological types *
- Possible anatomical sites
Cholangiocarcinoma: tumours of ductular epithelium of intra- or extrahepatic bile ducts
adenocarcinoma (>90%), SCC
Site:
□ Intrahepatic (<10%): above CHD bifurcation
□ Perihilar (Klatskin, 50%): from CHD bifurcation to cystic duct origin
□ Distal (40%): distal to cystic duct origin (i.e. CBD)
Anatomical classification of Perihilar Cholangiocarcinoma /
Bismuth-Corlette classification for perihilar tumours:
□ Type I: below confluence of L/R hepatic ducts
□ Type II: reaching confluence
□ Type IIIa/b: involve CHD + R/L hepatic ducts
□ Type IV: multicentric or involve CHD + RHD + LHD
Cholangiocarcinoma *
HPB risk factors
- *Primary sclerosing cholangitis** and UC
- *Recurrent pyogenic cholangitis** (hepatolithiasis)
- *Parasitic infection:** Clonorchis, Opisthorchis
- *Gallstones**
- *Chronic liver disease**
Multiple biliary papillomatosis
Fibropolycystic liver diseases
Cholangiocarcinoma *
Extra-HPB risk factors
FAT:
- *Diabetes mellitus**
- *Obesity and metabolic syndrome**
- *INFECTED:**
- *HIV infection**
- *H. pylori infection**
Lynch syndrome
Cystic fibrosis
Compare symptoms and signs of Intra-hepatic and extra-hepatic Cholangiocarcinoma /
Ddx intrahepatic cholangiocarcinoma
Benign:
Hepatic adenoma
Hepatic haemangioma
Focal nodular hyperplasia
Malignant
Hepatocellular carcinoma
Metastasis to liver
Ddx extra-hepatic cholangiocracinoma /
Benign:
CBD stones
Post-instrumentation strictures
Sclerosing cholangitis (PSC, IgG4-related)
Chronic pancreatitis (compress CBD)
Malignant
CA ampulla and duodenum
CA head of pancreas
Malignant hilar nodes
3 patterns of cholangiocarcinoma spread /
List curative and palliative treatment options for cholangiocarcinoma *
Curative:
- Hepatectomy
- Bile duct excision + reconstruction
- Hilar/ Portal Lymph node clearance
- Pancreaticoduodenectomy (Whipple’s) if distal disease
± adjuvant chemo/RT
- *Palliative:**
- Radiotherapy
- Chemotherapy: GP regimen: cisplatin + Gentamycin chemo irradiation
- Metallic stenting: Plastic vs metallic
- Surgical bypass: Hepaticojejunostomy (HJ)
- Drainage: PTBD or ERCP
Indication for portal vein embolization for cholangiocarcinoma /
- Future left lateral section <30% of estimated total liver volume (Urata formula)
Recurrent pyogenic cholangitis
definition *
Causes
Recurrent cholangitis caused by stone formation resulting in stricturing of biliary tree and biliary obstruction
Causes:
1. Bacterial infection: Gram -ve bacilli
• Escherichia coli
• Klebsiella sp.
• Proteus sp.
• Pseudomonas aeruginosa
Anaerobes
2. Parasitic infection
Major liver trematodes or flukes that infect humans
• Clonorchis sinensis
• Opisthorchis viverrini
• Fasciola hepatica
- *Roundworms**
- *• Ascaris lumbricoides**
RPC /
Pathogenesis
Stasis + Stricturing + Recurrent infection
Infection of bile ducts
>> Inflammation of portal triad and hepatocyte necrosis
>> Cholangiohepatitis, fibrosis and cholangitis with abscess formation
>> Bilirubinate stones and stricture formation
RPC
Demographics /
exclusively in people who live in Southeast Asia
equal frequency in males and females
peak prevalence in 30 – 40s
Lower socio-economic group
RPC
Typical locations of stricture formation /
Left main heaptic duct, segmental ducts
RPC *
S/S
Charcot’s triad
• Fever
o With or without chills
• Abdominal pain
o RUQ or epigastric pain
• Jaundice
RPC
First-line investigations: *
USG abdomen/ Liver USG: stones, ductal dilatation, liver abscess
Typical site:
- Predilection to left main hepatic duct and segmental ducts
- Majority cause left hepatic lobe atrophy
CT abdomen
MRCP/ MRI
ERCP/ PTC with prophylactic antibiotics to prevent cholangitis or sepsis
RPC
Supportive and definitive treatment options *
Aims of definitive treatment
- *- IV antibiotics**
- *- Rehydration and analgesics**
- *- Urgent biliary decompression by ERCP**: with sphincterotomy, stricture dilatation and placement of biliary endoprosthesis (stent)
- Hepaticojejunostomy with anastomosis into small bowel/ Hepaticojejunostomy with cutaneous stoma**
Aims:
- *Remove biliary stones**
- *Enlarge strictures/ Bypass strictures** for adequate biliary drainage
- *Permanent percutaneous access to biliary tract**
RPC *
Complications
Hepatobiliary complications
- Secondary biliary cirrhosis
- Cholangiocarcinoma
- Portal vein thrombosis
- Liver failure
Specific complications of RPC
- Biliary sepsis
- Pancreatitis: passage of biliary stones
- Rupture of obstructed pus-filled bile ducts into peritoneum
- Abscess formation: Liver abscess or abscess at distant sites including lungs and brain
- Fistulization: choledocho-duodenal fistula into gastrointestinal tract or abdominal wall
Liver abscess *
Risk factors
RFs:
□ Diabetes mellitus: classically a/w Klebsiella pneumoniae
□ Underlying HBP disease, eg. recurrent pyogenic cholangitis, liver transplant, liver cirrhosis
□ Colorectal cancer
□ Others: chronic PPI use, immunocompromised state (eg. CGD)
Liver abscess /
Potential routes of infection
Ascending biliary infection: Biliary tract disease, Ascending cholangitis, empyema of GB, gallstones, malignant obstruction…etc
Portal vein pyemia: Intestinal pathology, Acute appendicitis, diverticulitis, pylephlebitis, Crohn’s disease
External inoculation: Penetrating wounds or iatrogenic
Hematogenous seeding: systemic bacteremia
Liver abscess
S/S *
Complications (3)
□ Fever (90%): spiking fevers with chills
□ RUQ pain (89-100%): due to liver capsule stretch, may radiate to shoulder
□ Other liver symptoms: jaundice (23-43%), hepatomegaly (51-92%)
□ Constitutional symptoms: anorexia, weight loss, malaise
Complications:
→ Abscess rupture (3.8%)
→ Pleuropulmonary Cx (15-20%)
→ Local compression: Budd-Chiari syndrome (IVC/hepatic vein)
→ Consult EYE for K. pneumoniae endophthalmitis
Ddx fever + RUQ pain *
(1) Hepatitis
(2) Acute cholangitis
(3) Acute cholecystitis
(4) RLZ pneumonia
(5) :Liver abscess
Liver abscess /
First-line investigations
Basic blooods: NcNc anaemia, leukocytosis + L-shift, ↑ALP/GGT (SOL pattern) ± ↑bilirubin/AST, ↑CRP
Blood culture
Stool/serology for Entamoeba histolytica
USG: round/ovoid hypo/hyperechoic mass with internal echoes
Contrast CT: irregular lesion with central hypodensity ± gas
Double target sign: central hypodensity with hyperdense rim (capsule) and surrounding hypodensity (oedema)
MRI: T1W hypointense, T2W hyperintense
Liver abscess *
First-line treatment
Supportive: resuscitate, vitals..etc
- *Percutaneous drainage: diagnostic + therapeutic****
- needle aspiration (if small ≤5cm) or catheter placement (if large >5cm)
- USG- (small/superficial) or CT-guided
Surgical drainage: can be open or laparoscopic (rarely done, high mortality)
Antibiotics: empirically give ceftriaxone + metronidazole/gentamicin for 4-6 weeks until fever and biochemical profile subsides
Pancreatic Cancer *
Demographic
Risk factors - pancreatic and systemic RF
Demography:
Median age 65, slight Male predominance
Pancreatic risk factors:
- *- Chronic pancreatitis**
- Pancreatic premalignant conditions: e.g. Pancreatic intraepithelial neoplasia (PanIN), Intraductal papillary mucinous neoplasm (IPMN)
- Familial Pancreatic CA (FPC)
- Genetic predisposition: e.g. Hereditary pancreatitis (PRSS1, SPINK1), Hereditary breast-ovarian cancer (BRCA1/2)
Systemic risk factors:
- *Lifestyle factors:** smoking, obesity, DM
- *Infections: H.pylori, HBV/HCV**
Pancreatic cancer /
Pathological subtypes
□ Ductal adenocarcinoma (85%): signet ring, adenosquamous, anaplastic, colloid
- Pancreatic intraepithelial neoplasia (PanIN)
□ Cystic neoplasms: malignant potential for IPMN/MCN
- Serous cystadenoma
- Mucinous cystic neoplasm (MCNs)
- Intraductal papillary mucinous neoplasms (IPMN):
Pancreatic cancer /
Possible anatomical locations
□ Head (60%): a/w better prognosis (earlier detection due to obstructive jaundice)
□ Body (15%) or tail (5%): a/w worse prognosis (late detection)
□ Diffuse (20%)
Pancreatic cancer /
S/S specific to pancreatic head cancer vs pancreatic tail cancer
Head:
- Painless progressive obstructive jaundice
- Vague epigastric/RUQ discomfort
- S/S of pancreatic insufficiency with New onset diabetes (Steatorrhoea, maldigestion, malabsorption)
- S/S of Gastric outlet obstruction
Tail:
- Severe epigastric pain radiating to the back (⸪ invasion of coeliac and mesenteric plexus)
- S/S of pancreatic insufficiency with New onset diabetes (Steatorrhoea, maldigestion, malabsorption)
- Constitutional symptoms and S/S of metastasis
Pancreatic cancer /
Paraneoplastic manifestations
Paraneoplastic manifestations (notorious)
Trousseau’s syndrome (6%): unexplained migratory superficial thrombophlebitis
Paraneoplastic pemphigoid
Panniculitis (rare): esp in acinar cell variant, usu on legs
Systemic metastasis: liver, peritoneum, lungs, bone (less common)
Constitutional symptoms: malaise, weight loss, anorexia
Pancreatic cancer *
Diagnostic investigations and typical findings
- *TAUS: i**nitial screening Ix
- Pancreatic mass: focal hypoechoic hypovascular solid mass with irregular margins
CT abdomen with pancreas protocol
→ Ill-defined hypoattenuating mass
→ Double duct sign
ERCP
→ Findings: double duct sign, >1cm pancreatic duct stricture
MRCP: same as ERCP
Tissue biopsy: imaging guided, for non-operative/ neoadjuvant Tx
DDx pancreatic mass *
Pancreatic neuroendocrine tumours
Pancreatic lymphoma
Focal chronic pancreatitis
Autoimmune pancreatitis
Definitive surgical treatment options for Pancreatic cancer: head vs tail *
- *Pancreatic Head:**
- *- Radical Pancreaticoduodenectomy (Whipple’s operation) + Reconstruction by Roux-en-Y**
- *Pancreatic Tail:**
- *- Distal/central subtotal pancreatectomy ± splenectomy**
No safe resection margin
- Total pancreatectomy
Detail of Whipple’s procedure and Roux-en-Y reconstruction: list all resections and anastomoses /
En-bloc resection of 6 structures:
- Head of pancreas
- SB: duodenum + first 15cm of jejunum
- *- Common bile duct**
- *- Gallbladder**
- *- Stomach**: distal gastrectomy
- Regional LNs
Reconstruction by roux-en-Y (3 anastomoses)
- *- PJ/G:** distal pancreas to jejunum/stomach
- HJ: hepatic duct to jejunum (45-60cm proximal to GJ)
- GJ: stomach to jejunum
Post-Whipple supportive treatment (check) /
Pancreatic drain
Broviac catheter
Parenteral nutrition
Treatment options for unrectable pancreatic cancer *
Systemic therapy: radiotherapy, chemotherapy
→ Chemotherapy (1st line): FOLFIRINOX, gemcitabine monotherapy
→ Other options (2nd line): other chemotherapy
Palliative drain: Metallic drain
- *Surgical bypass**
- Biliary bypass for obstructive jaundice + Coeliac axis block: Gastrojejunostomy and Hepaticojejunostomy
- Triple bypass if obstructive jaundice + GOO
Tests to differentiate liver primary vs secondary metastasis /
IHC tests
Lung primary= TTF1
Colorectal primary = CDX2
Breast primary = BRST2
Gynaecological primary = CA125
