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Acute Pancreatitis

Definition

Acute pancreatitis is an acute inflammatory process of the pancreas with varying involvement of local tissues or remote organ systems.

Aetiology:

• Most cases can be attributed to one of two causes:

Gallstones

• Three Main Theories of How Gallstones Trigger Pancreatitis:
1. Ampullary Obstruction: A gallstone lodges in the ampulla of Vater, blocking pancreatic juice drainage, leading to increased pressure and inflammation.
2. Local Inflammation: The stone irritates surrounding tissues, causing inflammation that extends to the pancreas.
3. Transient Bile Reflux: Partial obstruction may cause bile to reflux into the pancreatic duct, resulting in irritation and inflammation.

Alcohol Consumption/Excess

The exact mechanism is not fully understood. Hypotheses include:

• Toxic Effects on Pancreatic Cells:
  • Alcohol and its byproducts (e.g., acetaldehyde) directly damage pancreatic acinar cells.
  • This toxicity leads to oxidative stress, inflammation, and cell death.
• Increased Digestive Enzyme Activation:
  • Normally, digestive enzymes are inactive in the pancreas but become active in the small intestine; alcohol may trigger premature activation, causing autodigestion.
• Thickened Secretions and Blocked Ducts:
  • Alcohol increases the protein content of pancreatic secretions, forming plugs that block ducts, leading to backpressure and inflammation.
• Increased Sensitivity to Other Triggers:
  • Alcohol weakens the pancreas, making it more susceptible to damage from other factors like a high-fat diet or gallstones.
• Changes in Gut-Liver-Pancreas Interaction:
  • Alcohol alters the gut microbiome and increases intestinal permeability, allowing toxins to reach the pancreas and trigger inflammation.
• Disruption of Blood Flow:
  • Chronic alcohol use may constrict blood vessels, reducing oxygen supply and predisposing the pancreas to injury.

Other Causes of Acute Pancreatitis

Other less common causes can be remembered with the mnemonic: I GET SMASHED

Pathophysiology

Trigger to Pancreatitis

• The exact mechanism of pancreatic cell injury remains unclear.
• Local inflammation ensues following the initial insult.
• The inflammatory process may remain local or become systemic.
• Systemic inflammatory cytokines can lead to multi-organ dysfunction.

Clinical Presentation

History

• Patients typically report worsening epigastric pain radiating to the back.
• The pain is often relieved by leaning forward.
• Some patients report prior dull right upper quadrant pain (possibly due to gallstones).
• Nausea and vomiting may occur.

Examination Findings

• Findings range from localized epigastric tenderness to generalized peritonitis.
• In severe cases, signs of cardiovascular or respiratory dysfunction may be present.
• Retroperitoneal bleeding may be evident with:
  • Cullen's Sign: Umbilical bruising.
  • Grey Turner's Sign: Flank bruising.

Diagnosis

How to Diagnose Pancreatitis

• Diagnosis is based on 2 out of 3 criteria:
  1. Serum amylase/lipase elevation (3x normal or significant rise)
  2. Characteristic clinical presentation
  3. CT imaging evidence

A Note on Serum Amylase

• Correlation with clinical and imaging findings is crucial since amylase may be elevated in other conditions:
• Mesenteric infarction
• GI perforation
• Acute cholecystitis
• Diabetic ketoacidosis
• Viral infections
• A normal amylase does not rule out pancreatitis, especially in delayed presentations.

The Use of Serum Lipase

• Lipase is more sensitive and specific than amylase and remains elevated longer.
• Its use may be limited due to cost.

Initial Management of Acute Pancreatitis

• Management is supportive with aggressive fluid resuscitation due to third spacing.
• Monitor vital signs and urine output; involve intensive care if needed.

Severity Scoring

• Severity scoring systems (e.g., Glasgow, Ranson, APACHE II) help predict outcomes.

Glasgow Scoring System

Remember the mnemonic "PANCREAS":

Preventing Further Episodes

Look for Gallstones

• Ultrasound is recommended to detect gallstones.
• If negative and suspicion remains, consider EUS or MRCP.
• If gallstones are found, a cholecystectomy should be performed during the same admission if possible.

Alcohol Intake

• Strict cessation of alcohol is the most effective prevention.

Assessment for Other Causes

• If no obvious cause is found, further investigation is warranted.

Supportive Care

Fluid Balance

• Monitor fluid balance rigorously; aggressive IV fluids are required.
• Monitor urine output, blood pressure, and lactate levels.
• Avoid over-resuscitation in patients with cardiopulmonary issues.

Monitoring for Complications

• A CT scan is recommended in patients with prolonged symptoms or biochemical abnormalities.
• CT is ideally performed after 72 hours from symptom onset.

Pain Management

• Effective pain control is critical to prevent respiratory complications.
• PCA may be used in severe cases.
• Avoid NSAIDs to reduce the risk of renal impairment or GI bleeding.

Nutritional Support

• Mild cases: Early oral feeding once nausea subsides.
• Moderate-to-severe cases: Enteral nutrition within 24–48 hours if oral intake is not possible.
• TPN is reserved for cases where enteral feeding is contraindicated.

Complications of Acute Pancreatitis

Systemic Complications

• Acute pancreatitis increases the risk of AKI, ARDS, and distributive shock requiring ICU admission.

Local Complications

Atlanta classification of pancreatitis complications

Pancreatic Necrosis

What is Pancreatic Necrosis?

• Localized or diffuse non-viable pancreatic tissue due to severe inflammation, ischemia, and autodigestion.
• Necrosis is typically sterile, but infection increases mortality.
• Antibiotic prophylaxis is not recommended unless infection is confirmed.

What Tissue is Necrotic?

• Parenchymal necrosis: Primarily pancreatic tissue (worse outcomes, ~5%).
• Peripancreatic necrosis: Often associated with better outcomes (~20%).
• Combined necrosis: Most common (~75%).

Infection of Necrotic Tissue

• Two-thirds of necrotic collections remain sterile.
• If infection occurs, mortality increases to 20–30%.
• Indicators include elevated procalcitonin, positive blood cultures, CT guided aspiration, and gas in necrotic tissue.

Diagnosing Pancreatic Necrosis

• CT scan with portal venous contrast is the gold standard.
• MR pancreas can differentiate between solid and liquid necrosis.

Management of Pancreatic Necrosis

• Most sterile necrotic collections resolve with conservative management.
• Intervention is indicated if there is mechanical obstruction or if infected necrosis fails to respond to antibiotics.

Interventions for Pancreatic Necrosis

• Surgical Management:
  • Open necrosectomy is the standard approach but carries high mortality (~25%) and fistula risk.
  • Laparoscopic necrosectomy may reduce mortality and risk of multi-organ failure.
• Percutaneous Approach:
  • Percutaneous drainage under US or CT guidance (preferably retroperitoneal) minimizes complications.
  • Success rate is around 55.7% with a mortality rate of 15.4% in infected cases.
• Endoscopic Approach:
  • Drainage via puncture through the gastric or enteric wall under ultrasound guidance.
  • A stent is placed after tract dilation to allow drainage.
  • Mechanical debridement may be performed for more solid necrosis.
  • Irrigation (e.g., with hydrogen peroxide) may reduce the need for repeat procedures.

Pancreatic Pseudocyst

What is a Pseudocyst?

• A well-defined collection of pancreatic fluid that appears after 4 weeks of symptom onset.
• Called "pseudo" because it lacks an epithelial lining.

Aetiology of Pseudocysts

• Disruption of the pancreatic duct leads to extravasation of fluid and pseudocyst formation.

Complications of a Pseudocyst

• Haemorrhage: Erosion of nearby vessels can cause life-threatening bleeding; managed via interventional radiology.
• Infection: Can occur spontaneously or post-procedure; treated with antibiotics and drainage.
• Biliary Obstruction: A large cyst in the head may obstruct the CBD, causing jaundice and cholangitis.
• Gastric Outlet Obstruction: Compression of the stomach may cause early satiety or obstruction.
• Portal Hypertension: Compression of splenic or portal veins can increase portal pressure.

Management of Pseudocysts

• Most small pseudocysts resolve spontaneously and require only imaging surveillance.
• Complicated pseudocysts require drainage, usually via a cystogastrostomy.
• Endoscopic stenting (e.g., Hot Axios) is now preferred over open surgery.
• The stent remains in place for at least 6 weeks, and is removed after resolution.

Long Term Complications of Pancreatitis

Endocrine Insufficiency

• Recurrent or severe pancreatitis may destroy beta-cells, resulting in pancreatogenic (Type 3C) diabetes.
• This condition is irreversible.

Exocrine Insufficiency

• Loss of pancreatic tissue can impair enzyme secretion, causing malabsorption and steatorrhea.
• Management involves pancreatic enzyme replacement therapy (PERT) such as Creon.
• Some patients may eventually regain function and wean off PERT.

Pancreatic Cancer

Definition

Pancreatic cancer is a highly aggressive malignancy, most commonly pancreatic ductal adenocarcinoma (PDAC, ~90%). It has a poor prognosis due to late presentation and early metastasis.

Epidemiology

• Incidence: ~10-15 per 100,000/year (UK).
• Age: Peak >70 years.
• Sex: Slight male predominance.
• Risk factors:
  • Modifiable: Smoking, obesity, alcohol (via chronic pancreatitis).
  • Non-modifiable: Chronic pancreatitis, diabetes mellitus, family history, genetic syndromes (BRCA2, Lynch, Peutz-Jeghers).

Pathophysiology

• Common mutations:
  • KRAS (90-95%) – oncogenic driver.
  • TP53 (50-75%) – tumour suppressor loss.
  • CDKN2A (p16 inactivation).
  • SMAD4 (loss in ~55%) – associated with metastasis.
• Spread:
  • Local invasion → Bile duct, duodenum, stomach, nerves (severe pain).
  • Lymphatic → Peripancreatic and para-aortic nodes.
  • Hematogenous → Liver (most common), lungs, peritoneum.

Clinical Features

Classic Presentation:

• Painless obstructive jaundice (head of pancreas tumours).
• Epigastric pain (body/tail tumours, radiates to back, worse at night).
• Unexplained weight loss & anorexia.

Courvoisier’s Law

If a patient has painless jaundice + a palpable gallbladder, the cause is likely malignant biliary obstruction (e.g., pancreatic cancer).

Diagnosis

• Blood Tests: ↑ ALP, ↑ GGT, ↑ bilirubin, CA 19-9.
• Imaging:
  • CT pancreas (triple-phase contrast): Gold standard for diagnosis & staging.
  • Endoscopic ultrasound (EUS) + biopsy: Best for histological confirmation.

Histopathology

• Macroscopic: Firm, gritty mass (head of pancreas most common).
• Microscopic:
  • Irregular glandular structures in a desmoplastic (fibrotic) stroma.
  • Perineural invasion (causes severe pain).

Management

• Surgical:
  • Whipple’s procedure (pancreaticoduodenectomy) → For head tumours.
  • Distal pancreatectomy → For body/tail tumours.
• Non-Surgical:
  • Neoadjuvant chemotherapy: FOLFIRINOX for borderline resectable cases.
  • Palliative chemotherapy: FOLFIRINOX or gemcitabine ± nab-paclitaxel.
• Supportive Care: Biliary stenting (ERCP), pain management, enzyme replacement.

Prognosis

• Resectable disease: 5-year survival 15-25%.
• Locally advanced: <5%.
• Metastatic: ~1% (median survival 3-6 months).

Key Takeaways

• **Painless jaundice + Courvoisier’s sign** → Suspect pancreatic cancer.
• **CT scan** is the gold standard for diagnosis.
• **Surgery is the only curative option**, but most present late.

Benign Pancreatic Lesions

1. Cystic Lesions

(A) Pseudocysts (Inflammatory, Non-Neoplastic)

• Definition: Fluid-filled collections lacking an epithelial lining, usually after pancreatitis.
• Composition: Enzyme-rich fluid (high amylase, lipase), fibrous capsule, no epithelium.
• Formation: Ductal injury → Fluid leakage → Fibrosis & encapsulation → Cyst formation.
• Key Point: Pseudocysts are not true cysts.

(B) Serous Cystadenoma (SCA) – True Benign Neoplasm

• Definition: Benign neoplasm of glycogen-rich cuboidal epithelial cells.
• Composition: Microcystic pattern, clear serous fluid, no mucin.
• Formation: Linked to VHL mutations.
• Key Point: Always benign, no treatment needed unless symptomatic.

(C) Mucinous Cystic Neoplasm (MCN) – Pre-Malignant

• Definition: Cystic neoplasm with malignant potential, mostly in women.
• Composition: Thick-walled mucin-filled cyst, lined by mucinous epithelium.
• Formation: Mucin accumulation → Cyst expansion → Possible malignancy.
• Key Point: Requires surgical resection if >4 cm.

(D) Intraductal Papillary Mucinous Neoplasm (IPMN) – Pre-Malignant

• Definition: Mucin-producing neoplasm within the pancreatic ducts.
• Composition: Cystic dilation, mucin-secreting papillary epithelium.
• Formation: KRAS/GNAS mutations lead to excess mucin & ductal dilation.
• Key Point: Can progress to cancer; requires surveillance or surgery.

2. Solid Lesions

(A) Pancreatic Neuroendocrine Tumours (PNETs)

• Definition: Arise from pancreatic islet cells, can be hormone-secreting.
• Formation: Neoplastic transformation → Excess hormone secretion.
• Key Point: Functional PNETs require surgical resection.

(B) Solid Pseudopapillary Tumour (SPT) – Low-Grade Malignancy

• Definition: Rare pancreatic neoplasm, primarily in young women.
• Composition: Cystic + solid architecture, β-catenin mutation.
• Key Point: Surgical removal is curative.

(C) Fibromas & Lipomas – True Benign Tumours

• Definition: Soft tissue tumours, composed of fibroblasts/adipocytes.
• Management: No treatment unless symptomatic.

Whipple’s Procedure (Pancreaticoduodenectomy)

Whipple’s procedure is a major surgical operation performed to remove the head of the pancreas, parts of the duodenum, bile duct, gallbladder, and sometimes a portion of the stomach. It is primarily used to treat pancreatic head cancer and other periampullary malignancies, as well as select benign conditions.

1. Indications

Malignant Conditions

• Pancreatic head adenocarcinoma (most common)
• Ampullary carcinoma
• Distal cholangiocarcinoma (bile duct cancer)
• Duodenal adenocarcinoma
• Neuroendocrine tumours (e.g., insulinoma, gastrinoma)
• Metastatic renal cell carcinoma to the pancreas

Benign Conditions

• Chronic pancreatitis (in selected cases)
• Benign pancreatic head tumours (IPMN, SPT, cystic neoplasms)
• Duodenal trauma (rare indication)

2. Anatomy Involved

• Pancreas (head, uncinate process)
• Duodenum (first and second parts, sometimes third)
• Common bile duct (distal portion)
• Gallbladder
• Stomach (partial removal in classic Whipple)
• Vascular structures (SMA, SMV, portal vein)

3. Surgical Procedure

Step 1: Resection

1. Kocherisation: Mobilize the duodenum and pancreatic head.
2. Division of the bile duct: At or above the level of the cystic duct.
3. Resection of the duodenum: Typically including the first and second parts.
4. Partial gastrectomy (Classic Whipple) or Pylorus Preservation (PPPD).
5. Transection of the pancreas: At the neck, anterior to the SMV.
6. Lymphadenectomy: Regional lymph node dissection.

Step 2: Reconstruction

1. Pancreaticojejunostomy: Anastomosis of the pancreatic remnant to the jejunum.
2. Hepaticojejunostomy: Anastomosis of the common hepatic duct to the jejunum.
3. Gastrojejunostomy: To restore gastrointestinal continuity (if a classic Whipple is performed).

4. Variants of Whipple’s Procedure

• Classic Whipple: Involves partial gastrectomy.
• Pylorus-Preserving Pancreaticoduodenectomy (PPPD): Preserves the pylorus, reducing postoperative dumping syndrome.

5. Complications

Early Postoperative Complications

• Pancreatic fistula: Due to anastomotic leak.
• Delayed gastric emptying
• Bile leak
• Haemorrhage: Intra-abdominal, anastomotic, or from pseudoaneurysm.
• Postoperative infections: Intra-abdominal abscess, wound infection, cholangitis, pneumonia.

Late Complications

• Diabetes mellitus: Due to pancreatic insufficiency.
• Malabsorption and steatorrhea: Resulting from exocrine insufficiency.
• Dumping syndrome: Particularly if gastrectomy is performed.
• Biliary strictures

6. Prognosis and Survival

• Pancreatic cancer: 5-year survival post-Whipple ranges from 20–25%, with better outcomes in early-stage disease.
• Other periampullary cancers: Generally have a better prognosis than pancreatic adenocarcinoma.
• Benign conditions: Whipple’s can be curative, though long-term morbidity may be significant.

7. Postoperative Management

• Early mobilisation and physiotherapy
• Nutritional support: TPN if necessary, transitioning to gradual oral intake.
• Pancreatic enzyme replacement therapy (PERT): For exocrine insufficiency.
• Diabetes management: If endocrine function is impaired.
• Surveillance: For recurrence (using CT scans, tumor markers like CA 19-9).

Summary

• Whipple’s procedure is the primary surgical treatment for pancreatic head and periampullary cancers.
• It involves en bloc removal of the pancreatic head, duodenum, gallbladder, and bile duct with reconstruction.
• Postoperative complications, especially pancreatic fistula, require close monitoring.
• Survival depends on tumor type, stage, and resectability.