Pancreatic and biliary disease

Question 1

Bile duct dilatation

Answer 1

Clinical features:

• RUQ pain
• jaundice

All causes of bile duct dilatation lead to cholestatic symptoms once obstruction becomes severe enough. The classic symptoms and signs are jaundice, pruritus, pale stools, and dark urine. Typically, choledocholithiasis is associated with acute intermittent right upper quadrant pain and transient jaundice. Malignant causes of bile duct obstruction, such as carcinoma of the head of the pancreas, are often initially painless or manifest as dull pain, and jaundice is progressive. Occasionally, patients with bile duct strictures may develop manifestations of chronic cholestasis: xanthomas, anorexia, nausea, vomiting, weight loss, and deficiencies of calcium and fat-soluble vitamins.

Patients with biliary obstruction typically have elevated serum alkaline phosphatase and gamma-glutamyl transpeptidase levels. These enzymes are disproportionately elevated compared with serum transaminases. In more severe cases of biliary obstruction, total and conjugated bilirubin values are increased.

Patients with elevated levels of alkaline phosphatase and direct hyperbilirubinemia without biliary dilatation have intrahepatic cholestasis with blockage of biliary capillaries as a result of hepatocyte swelling.

Complete or partial bile duct obstruction leads to bile stasis. This can be complicated by ascending cholangitis and stone formation. Ascending cholangitis can be recurrent and life-threatening: the classic clinical manifestation is fever and rigors, jaundice, and right upper quadrant abdominal pain (Charcot’s triad). Patients also may have altered mental status and hypotension (Reynolds’ pentad). Benign causes of bile duct ob­struction are more likely to cause ascending cholangitis than malignant causes.

Imaging:

• Bile duct dilatation on USS is indicated by:
• intrahepatic bile ducts >2 mm
• extrahepatic bile ducts (common hepatic duct and common bile duct) >6 mm [+1 mm per decade above 60 years old] OR >10 mm post-cholecystectomy

Focal dilatation may be a result of downstream stricture, or damage to the elasticity of that segment of bile duct, possibly from prior stone passage.

Causes of intrahepatic duct dilatation:

• intrahepatic or hilar cholangiocarcinoma (e.g. Klatskin tumor)
• intrahepatic choledocholithiasis
• recurrent pyogenic cholangitis
• Caroli disease

Causes of extrahepatic (common hepatic duct, CBD) biliary dilatation:

• early choledocholithiasis
• sphincter of Oddi dyskinesia
• pregnancy
• choledochal cyst
• drugs (e.g. chronic opioid use)

Causes of intra AND extra hepatic biliary dilatation:

• pancreatic or ampullary mass (e.g. pancreatic ductal adenocarcinoma). Often also dilated main pancreatic duct. Periampullary tumors are the third most common type of gastrointestinal neoplasm, after colonic and gastric tumors. Adenocarcinoma of the pancreatic head results in generalized intrahepatic and extrahepatic bile duct dilatation to the level of obstruction
• choledocholithiasis. A stone in the distal common bile duct (CBD) results in generalized intrahepatic and extrahepatic bile duct dilatation to the level of obstruction
• pancreatitis. In chronic pancreatitis, changes seen inc: pancreatic atrophy, calcification, pancreatic duct dilatation seen as a “chain of lakes”
• external compression (e.g. Mirizzi syndrome, adenopathy)
• ascending cholangitis
• recurrent pyogenic cholangitis
• sclerosing cholangitis
• AIDS cholangiopathy
• choledochal cyst, type IV (rare)

Malignant causes of bile duct dilatation include the following:

• Pancreatic head carcinoma
• Cholangiocarcinoma
• Ampullary carcinoma
• Gallbladder carcinoma
• Hepatocellular carcinoma
• Malignant mucinous neoplasm of the pancreas or bile duct
• Lymphoma
• Metastatic disease

The most common malignant cause of bile duct dilatation is pancreatic adenocarcinoma, followed by cholangiocarcinoma. Seventy percent of pancreatic adenocarcinomas involve the head of the pancreas, where they may cause CBD dilatation in addition to pancreatic duct dilatation. The incidence of cholangiocarcinoma is at least four times less than pancreatic carcinoma. Cholangiocarcinoma complicates several benign diseases of the bile ducts, including choledochal cysts, PSC, and parasitic liver infestation. Thus, malignant and benign causes of biliary dilatation may coexist and differentiating one from the other may be problematic.

• https://radiologykey.com/dilated-bile-ducts/ (Dilated Bile Ducts)*
• https://www.ajronline.org/doi/pdf/10.2214/AJR.13.11288 (Abnormalities of the Distal Common Bile Duct and Ampulla)*

Question 2

Ampullary carcinoma

Answer 2

Epidemiology:

• 10% of all duodenal polyps are ultimately found to be adenomas, and the most common location is in proximity to the ampulla of Vater. These lesions are most common in elderly patients, and other than familial adenomatosis coli, no other clear risk factors for the development of ampullary adenomas have been described in the literature.
• Up to 60% of ampullary adenomas are ultimately found to harbor at least some foci of invasive carcinoma

Pathogenesis:

• Periampullary tumors can originate from the pancreas, duodenum, distal common bile duct (CBD), or the structures of the ampullary (ampulla of Vater) complex
• Ampullary carcinomas are defined as those that arise within the ampullary complex, distal to the bifurcation of the distal CBD and the pancreatic duct
• Primary ampullary adenomas and carcinomas is more likely to arise from intestinal rather than pancreaticobiliary neoplasms.

Ampulla of vater anatomy:

• The ampulla of Vater is formed by the duodenal aspect of the sphincter of Oddi muscle, which surrounds the confluence of the distal CBD and main pancreatic duct, as well as the papilla of Vater, a mucosal papillary mound at the distal insertion of these ducts on the medial wall of the duodenum.

Presenting features:

• obstructive jaundice (80% of cases) caused by compression of the distal bile duct by the tumor
• Additional symptoms may include diarrhea due to fat malabsorption (steatorrhea), mild weight loss, and fatigue.
• Up to one-third of patients have chronic, frequently occult gastrointestinal blood loss with an associated microcytic anemia or heme-positive stools

DDx:

• benign tumors
• gallstones

Labs:

• LFTs show cholestatic picture

imaging:

• Abdo USS: first initial test to evaluate for gall stones. Will not show the tumor
• Abdo CT - visualise pancrease, determine degree of tumor invasion, assess for metastates
• ERCP: permits tumor diagnosis, biopsy, decompression (by placement of a stent)
• MRCP: performed if ERCP contraindicated (ppl with prior gastric surgery that makes ERCP technically challenging)
• EUS (endoscopic USS): not required, but is the most accurate for ‘T’ staging of ampullary tumors.

The distal common bile duct (CBD) and ampulla can be an extremely challenging location for the radiologist to assess. In any patient with a suspected pancreatobiliary abnormality, a dual-phase study with both arterial and venous phase images should be acquired. The arterial phase images are used to identify hypervascular tumors, subtle biliary tree mucosal hyperenhancement and thickening, and tumor neovascularity. The venous phase images are used to evaluate the liver and pancreas for traditionally hypovascular tumors and metastases, locoregional lymphadenopathy, and involvement of the venous vasculature by tumor

Question 3

Gall stone and biliary disease

Answer 3

Cholecystolithiasis:

• Cholecystolithiasis refers to the presence of stones in the gallbladder. The presence of stones in the gallbladder is not considered to be a disease unless they cause symptoms.
• uncomplicated gallstone disease refers to biliary colic in the absence of gallstone-related complications.
• complicated gallstone disease refers to gallstone-related complications which include acute cholecystitis, cholangitis, gallstone pancreatitis, gallstone ileus, and Mirizzi syndrome (impaction of a gallstone in the cystic duct, causing compression of the common bile or hepatic duct)

Biliary colic

• intense, constant, dull discomfort located in the right upper quadrant, epigastrium, or (less often) substernal area that may radiate to the back (particularly the right shoulder blade). Pain typically lasts at least 30 minutes, plateauing within an hour, an entire attack usually lasting less than six hours
• pain is often associated with diaphoresis, nausea, and vomiting
• Eating a fatty meal is a common trigger for gallbladder contraction, and many patients report postprandial pain.
• murphey’s negative
• Laboratory test results (complete blood count, aminotransferases, bilirubin, alkaline phosphatase, amylase, and lipase) are normal

Cholecystitis

• Inflammation of the gallbladder.
• Acute cholecystitis mostly occurs as a complication of symptomatic gallstones by cystic duct obstruction (acalculous cholecystitis occurs in 5-10% cases).
• Characterised by RUQ/epigastric pain (greater than 4-6hours), fever, and leukocytosis with increased bandforms (left shift). Murphey’s positive (sensitivity 97%, specificity 48% for acute cholecystitis).
• LFTs normal (given obstruction is limited to the gallbladder). Rarely mildly abnormal aminotransferase, amylase, bilirubin, jaundice due to the passage of sludge or pus.

If abnormal, consider choledocholithiasis, cholangitis, Mirizzi syndrome (a gallstone impacted in the distal cystic duct causing extrinsic compression of the common bile duct, and therefore causing abnormal LFTs as hepatic ducts affected too).

• Chronic cholecystitis describes chronic inflammatory cell infiltration of the gallbladder seen on histopathology. Thought to be a result of mechanical irritation or recurrent attacks of acute cholecystitis.
• Biliary USS: gallbladder wall thickening (>4-5mm) or edema (double wall sign), a sonographic Murphy’s sign, or failure of the gallbladder to fill during cholescintigraphy
• Abdo CT and MRCP done to rule out alternate diagnosis
• complications of cholecystitis: signs of sepsis (gangrenous cholecystitis i.e. necrosis of gall bladder wall), generalized peritonitis (perforation), abdominal crepitus (emphysematous cholecystitis esp with clostridium welchii), or bowel obstruction (gallstone ileus).

Choledocholithiasis:

Description:

• gall stones in the CBD. Mostly secondary cause due to the passage of gallstones from the gallbladder into the common bile duct.
• Primary choledocholithiasis (ie, formation of stones within the common bile duct) is less common. Typically occurs in the setting of bile stasis (eg, patients with cystic fibrosis).

Epidemiology:

• 5-20% pts have choledocholithiasis at the time of cholecystectomy

Presentation:

• biliary-type pain in right upper quadrant or epigastrium (but more prolonged than in typical biliary colic), nausea, and vomiting.
• pain from choledocholithiasis resolves when the stone either passes spontaneously or is removed
• Exam: Jaundice, RUQ tenderness, Courvoisier’s sign (a palpable gallbladder on physical examination)

Labs:

• ALT and AST are typically elevated early in the course of biliary obstruction
• later, LFTs typically develop cholestatic pattern (disproportionately elevated bilirubin, ALP, GGT)
• leukocytosis suggests cholangitis
• elevated pancreatic enzymes suggests pancreatitis

Imaging:

• transabdominal USS: evaluate for cholelithiasis, choledocholithiasis, and common bile duct dilation
• magnetic resonance cholangiopancreatography (MRCP)
• endoscopic ultrasound (EUS) +/- endoscopic retrograde cholangiopancreatography (ERCP)
• Intraoperative cholangiography or ultrasonography

Complications:

• acute gallstone pancreatitis: passage of gallstones obstructing flow from the pancreatic duct or by obstructing the ampulla, causing bile to reflux back into the pancreatic duct. Labs: elevated serum pancreatic enzyme levels, can have elevated bilirubin, ALP, transaminases (AST, ALT) when
• acute cholangitis: Charcot’s triad (fever, right upper quadrant pain, and jaundice) and leukocytosis. In severe cases, bacteremia and sepsis may lead to hypotension and altered mental status (Reynolds’ pentad)
• secondary biliary cirrhosis due to long-standing biliary obstruction (rare)

DDx:

• RUQ pain: uncomplicated gallstone disease, acute cholecystitis, sphincter of Oddi dysfunction, or functional gallbladder disorder
• Jaundice: liver disease, hematologic disorders, or biliary obstruction from any cause

Management:

• the management of choledocholithiasis is removal of the common bile duct stone either endoscopically or surgically.
• It is also important to identify and treat the complications of choledocholithiasis, such as acute pancreatitis and acute cholangitis.

Sphincter of Oddi dysfunction (SOD):

• may have biliary colic, but unlike patients with uncomplicated gallstone disease, patients with SOD have abnormal liver tests and/or dilation of the common bile duct.

Functional gallbladder disorder:

– Functional gallbladder disorder is a diagnosis of exclusion. Patients with functional gallbladder disorder have biliary colic, but do not have gallstones, sludge, or microlithiasis on abdominal imaging

Question 4

Pancreatitis

Answer 4

Acute pancreatitis

Severity classification:

● Mild acute pancreatitis: absence of organ failure and local or systemic complications

●Moderately severe acute pancreatitis: transient organ failure (resolves within 48 hours) and/or local or systemic complications without persistent organ failure (>48 hours)

●Severe acute pancreatitis: persistent organ failure that may involve one or multiple organs

Atlanta classification:

● Interstitial edematous acute pancreatitis: acute inflammation of the pancreatic parenchyma and peripancreatic tissues, but without recognizable tissue necrosis.

● Necrotizing acute pancreatitis: inflammation associated with pancreatic parenchymal necrosis and/or peripancreatic necrosis.

History:

• severe acute persistent upper abdominal pain. 90% of patients have associated nausea and vomiting which may persist for several hours. Dyspnea due to diaphragmatic inflammation, pleural effusions, or ARDS
• gallstone pancreatitis: pain is well localized and the onset of pain is rapid, reaching maximum intensity in 10 to 20 minutes.
• pancreatitis due to hereditary or metabolic causes or alcohol, the onset of pain may be less abrupt and the pain may be poorly localized.

Examination:

• epigastric tenderness on palpation (mild), or diffuse abdo tenderness (severe).
• Abdominal distention and hypoactive bowel sounds due to an ileus secondary to inflammation.
• scleral icterus due to obstructive jaundice due to choledocholithiasis or edema of the head of the pancreas
• Patients with severe pancreatitis may have fever, tachypnea, hypoxemia, and hypotension. Cullen’s signs or Grey turner sign (bleeding/echymosis due to retroperitoneal bleed from pancreatic necrosis)

Labs:

• Serum amylase — Serum amylase rises within 6 to 12 hours of the onset of acute pancreatitis. However has a short half-life of approximately 10 hours, and returns to normal in 3-5days
• Serum lipase has a sensitivity for acute pancreatitis ranging from 82-100%. Lipase rises within four to eight hours of the onset of symptoms, peaks at 24 hours, and returns to normal within 8 to 14 days. Diagnosis involves elevation in serum lipase or amylase to three times or greater than the upper limit of normal.
• elevations in C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF), and PMN elastase
• leukocytosis and an elevated hematocrit from hemoconcentration due to extravasation of intravascular fluid into third spaces.
• Metabolic abnormalities including elevated blood urea nitrogen (BUN), hypocalcemia, hyperglycemia, and hypoglycemia

Imaging:

• Abdo USS: pancreas appears diffusely enlarged and hypoechoic. Gallstones may be visualized in the gallbladder or the bile duct. Peripancreatic fluid in the setting of pancreatic necrosis
• Abdo CT: acute interstitial edematous pancreatitis. Necrosis of pancreatic tissue may also be seen. A pancreatic mass may be seen in patients with an underlying pancreatic cancer.
• AXR/CXR: colon cut off sign reflects a paucity of air in the colon distal to the splenic flexure due to functional spasm of the descending colon secondary to pancreatic inflammation. A ground glass appearance may indicate the presence of an acute peripancreatic fluid collection
• MRI: fat suppression, diffuse or focal enlargement of the pancreatic gland, the margins of the pancreas may be blurred. MRI has a higher sensitivity for the diagnosis of early acute pancreatitis as compared with contrast-enhanced abdominal CT

DDx:

• PUD
• choledocholithiasis or cholangitis. Serum ALT and AST are elevated. Bili/ALP are elevated.
• Cholecystitis. Mild elevations in serum aminotransferases and amylase, along with hyperbilirubinemia may be seen
• Perforated viscus
• bowel obstruction
• hepatitis

Management:

• Initial management of a patient with acute pancreatitis consists of supportive care with fluid resuscitation, pain control, and nutritional support.
• goal-directed therapy for fluid management. Initial fluid resusc and then slow IVFT (N/saline preferred if hypercalcemia present). Adequate fluid replacement can be assessed by an improvement in vital signs (HR <120, MAP 65 to 85 mmHg), urine output (>0.5 to 1 cc/kg/hour), reduction in hematocrit (target: 35 to 44%) and BUN over 24 hours. Fluid replacement has been associated with a reduction in morbidity and mortality in the first 12-24hrs. Inadequate hydration can lead to hypotension and acute tubular necrosis.
• Pain control: Opioids are safe and effective. Hydromorphone or fentanyl (IV)
• Serum glucose levels should be monitored hourly in patients with severe pancreatitis and hyperglycemia (BSL >18-20) should be treated as it can increase the risk of secondary pancreatic infections.
• Nutrition: In the absence of ileus, nausea or vomiting, oral feeding can be initiated within 24 hours as tolerated. In moderately severe to severe pancreatitis, oral feeding may not be tolerated due to postprandial pain, so they should commence enteral feeds (high protein, low fat, semi-elemental feeding formulas). Parenteral nutrition should be initiated only in patients who do not tolerate enteral feeding
• When an infection is suspected, antibiotics should be started. Prophylactic antibiotics are not recommended in patients with acute pancreatitis, regardless of the type (interstitial or necrotizing) or disease severity (mild, moderately severe, or severe)
• EUS or MRCP should be performed to determine the need for ERCP in the patients with: (1) Persistently elevated LFTS and/or dilation of common bile duct without overt cholangitis, (2) Pregnant patients, (3) Altered anatomy that would make an ERCP technically challenging
• Cholecystectomy should be performed after recovery in all patients with gallstone pancreatitis including those who have undergone an endoscopic sphincterotomy

Question 5

Pancreatic Cancer

Answer 5

Description:

• ductal adenocarcinoma of the exocrine pancreas
• 60-70% exocrine pancreatic cancers are localised to head of pancreas, 20-25% body/tail

Epi:

• exocrine pancreatic cancer is the 4th leading cause of cancer-related death in the US. Highly lethal
• frequently associated with delayed presentation, so only 15-20% of patients are candidates for pancreatectomy.

Clinical features:

• Commonly present with abdo/back pain (most frequently reported symptom, insidious onset), concurrent pancreatitis, jaundice, weight loss, night sweats, steatorrhoea (pale stools due to pancreas inability to produce fat digesting enzymes), asthenia (weakness), anorexia, dark urine.
• Examination: jaundice, hepatomegaly, RUQ mass, cachectic, Courvoisier’s sign (nontender but palpable distended gallbladder at the right costal margin), Epigastric mass
• skin eruptions are a rare finding (cicatrical, bullous pemphygoid, pancreatic panniculitis), supraclavicular metastases (Virchow’s node), and palpable periumbilical mass (Sister Mary Joseph’s node)
• Clues suggesting the possibility of a primary pancreatic lymphoma include a lack of jaundice (initially, until biliary obstruction occurs), the presence of constitutional symptoms (weight loss, fever, and night sweats), an elevated serum lactate dehydrogenase (LDH) or beta-2 microglobulin level, and a normal serum carbohydrate antigen 19-9 (CA 19-9)

Investigations:

• high LDH or beta-2 microglobulin, normal CA 19.9
• histology is the only way to distinguish with certainty a primary pancreatic cancer from a less common periampullary malignancy
• CT (sensitivity 89-97% for pancreatic ca)
• ERCP (diagnostic and treatment - stent insertion to relieve obstruction) or MRCP (for patients who can’t undergo ERCP). The “double duct sign” (dilatation of both CBD and pancreatic duct) is highly suggestive of malignancy.

Management:

• Surgical resection is the only potentially curative treatment

Prognosis:

• Prognosis is poor, even after a complete resection.
• 5-year survival after margin-negative (R0) pancreaticoduodenectomy is approximately 30% for node-negative and 10% for node-positive disease
  https: //www.uptodate.com/contents/clinical-manifestations-diagnosis-and-staging-of-exocrine-pancreatic-cancer?search=head%20of%20pancreas%20cancer&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

up to: “Pain is one of the most frequently reported symptoms, even with small (<2 cm) pancreatic cancers”