GI - Gallstones, Pancreatitis, Cholangiocarcinoma, RPC, Liver abscess, Pancreatic cancer

Question 1

Gallstones /

• Types
• Risk factors

Answer 1

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

Question 2

Screening for risk factors of gallstone disease in history taking *

Answer 2

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

Question 3

4 diseases stages of gallstone disease /

Answer 3

1. Lithogenic state: risk factors cause Microlithiasis suspended in bile
2. Asymptomatic GS: incidental finding on imaging
3. Symptomatic GS: Biliary colic +/- fat intolerance, dyspepsia
4. Complicated GS: Cholecystitis, CA gallbaldder, Cholangitis, Gallstone pancreatitis and ileus …etc

Question 4

Brief investigation and workup plan for Gallstone disease *

Answer 4

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

Question 5

Surgical treatment options of gallstone disease *

Answer 5

Laparoscopic cholecystectomy: Early or delayed LC

Gallbladder drainage:
Percutaneous transhepatic cholecystostomy
Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD)
Endoscopic transpapillary drainage by ERCP (ETGBD)

Question 6

Combination of surgical treatment options for CBD stone + Gallstones *

Answer 6

Pre-operative ERCP + Cholecystectomy: Most common

Laparoscopic cholecystectomy + Exploration of CBD: Emergency

Laparoscopic cholecystectomy + on-table ERCP

Question 7

Complications of gallstone disease *

Answer 7

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

Question 8

Acute pancreatitis /

Mild, moderate and severe presentation

Answer 8

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

Question 9

Scoring system for severity of acute pancreatitis *

Answer 9

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%

Question 10

Causes of acute pancreatitis and pathophysiology of each cause (9)

Answer 10

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

Question 11

Causative infective agents of acute pancreatitis *

Answer 11

Bacteria = Mycoplasma/ Legionella/ Leptospira

Virus = Mumps/ Coxsackievirus B/ HBV/ EBV/ CMV/ VZV/ HSV/ HIV

Fungi = Aspergillus

Parasites = Ascaris/ Clonorchis sinensis/ Toxoplasmosis/ Cryptosporidium

Question 12

Describe the anatomical location of 4 sections of pancreas /

Answer 12

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

Question 13

Arterial and venous supply of pancreas /

Answer 13

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)

Question 14

Complication of acute pancreatitis *

Answer 14

• *Pseudocyst**
• *Infected pseudocyst**
• *Necrotizing** pancreatitis
• *Hemorrhagic** pancreatitis

Pleural effusion

• *Ascites**
• *Splenic vein thrombosis**

Question 15

Pathophysiology of acute pancreatitis /

Answer 15

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

Question 16

Acute pancreatitis /

S/S

Answer 16

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

Question 17

Ddx acute pancreatitis /

Answer 17

Differential diagnosis
 Peptic ulcer disease
 Choledocholithiasis/ Cholangitis/ Cholecystitis
 Hepatitis
 Mesenteric ischemia
 Intestinal obstruction
 Myocardial infarction*

Question 18

Diagnostic criteria of acute pancreatitis /

Answer 18

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)

Question 19

Typical signs on abd. exam for acute pancreatitis /

Answer 19

• 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)

Question 20

Biochemical tests for acute pancreatitis /

Answer 20

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)

Question 21

Radiological tests for acute pancreatitis *

Features suggesting acute pancreatitis on each test

Answer 21

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

Question 22

First-line treatment of acute pancreatitis *

Answer 22

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

Question 23

First-line Surgical treatment options for acute pancreatitis *

Surgical options for complications

Answer 23

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

Question 24

Cholangiocarcinoma *

• Definition
• Histological types *
• Possible anatomical sites

Answer 24

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)

Question 25

Anatomical classification of Perihilar Cholangiocarcinoma /

Answer 25

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

Question 26

Cholangiocarcinoma \* HPB risk factors

Answer 26

* *Primary sclerosing cholangitis** and UC * *Recurrent pyogenic cholangitis** (hepatolithiasis) * *Parasitic infection:** Clonorchis, Opisthorchis * *Gallstones** * *Chronic liver disease** Multiple biliary papillomatosis Fibropolycystic liver diseases

Question 27

Cholangiocarcinoma \* Extra-HPB risk factors

Answer 27

**FAT:** * *Diabetes mellitus** * *Obesity and metabolic syndrome** * *INFECTED:** * *HIV infection** * *H. pylori infection** Lynch syndrome Cystic fibrosis

Question 28

Compare symptoms and signs of Intra-hepatic and extra-hepatic Cholangiocarcinoma /

Answer 28

Question 29

Ddx intrahepatic cholangiocarcinoma

Answer 29

Benign:  Hepatic adenoma  Hepatic haemangioma  Focal nodular hyperplasia Malignant  Hepatocellular carcinoma  Metastasis to liver

Question 30

Ddx extra-hepatic cholangiocracinoma /

Answer 30

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

Question 31

3 patterns of cholangiocarcinoma spread /

Answer 31

Question 32

List curative and palliative treatment options for cholangiocarcinoma \*

Answer 32

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

Question 33

Indication for portal vein embolization for cholangiocarcinoma /

Answer 33

- Future left lateral section \<30% of estimated total liver volume (Urata formula)

Question 34

Recurrent pyogenic cholangitis definition \* Causes

Answer 34

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**

Question 35

RPC / Pathogenesis

Answer 35

**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

Question 36

RPC Demographics /

Answer 36

exclusively in people who live in **Southeast Asia** equal frequency in males and females peak prevalence in **30 – 40s** **Lower socio-economic group**

Question 37

RPC Typical locations of stricture formation /

Answer 37

Left main heaptic duct, segmental ducts

Question 38

RPC \* S/S

Answer 38

**Charcot’s triad** • **Fever** o With or without chills **• Abdominal pain** o RUQ or epigastric pain **• Jaundice**

Question 39

RPC First-line investigations: \*

Answer 39

**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

Question 40

RPC Supportive and definitive treatment options \* Aims of definitive treatment

Answer 40

* *- 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**

Question 41

RPC \* Complications

Answer 41

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

Question 42

Liver abscess \* Risk factors

Answer 42

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)

Question 43

Liver abscess / Potential routes of infection

Answer 43

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

Question 44

Liver abscess S/S \* Complications (3)

Answer 44

□ **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

Question 45

Ddx fever + RUQ pain \*

Answer 45

(1) Hepatitis (2) Acute cholangitis (3) Acute cholecystitis (4) RLZ pneumonia (5) :Liver abscess

Question 46

Liver abscess / First-line investigations

Answer 46

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

Question 47

Liver abscess \* First-line treatment

Answer 47

**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

Question 48

Pancreatic Cancer \* Demographic Risk factors - pancreatic and systemic RF

Answer 48

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**

Question 49

Pancreatic cancer / Pathological subtypes

Answer 49

□ 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):

Question 50

Pancreatic cancer / Possible anatomical locations

Answer 50

□ 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%)

Question 51

Pancreatic cancer / S/S specific to pancreatic head cancer vs pancreatic tail cancer

Answer 51

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

Question 52

Pancreatic cancer / Paraneoplastic manifestations

Answer 52

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

Question 53

Pancreatic cancer \* Diagnostic investigations and typical findings

Answer 53

* *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

Question 54

DDx pancreatic mass \*

Answer 54

Pancreatic neuroendocrine tumours Pancreatic lymphoma Focal chronic pancreatitis Autoimmune pancreatitis

Question 55

Definitive surgical treatment options for Pancreatic cancer: head vs tail \*

Answer 55

* *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**

Question 56

Detail of Whipple's procedure and Roux-en-Y reconstruction: list all resections and anastomoses /

Answer 56

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

Question 57

Post-Whipple supportive treatment (check) /

Answer 57

Pancreatic drain Broviac catheter Parenteral nutrition

Question 58

Treatment options for unrectable pancreatic cancer \*

Answer 58

**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

Question 59

Tests to differentiate liver primary vs secondary metastasis /

Answer 59

IHC tests Lung primary= TTF1 Colorectal primary = CDX2 Breast primary = BRST2 Gynaecological primary = CA125