Murphy's Sign

Disclaimer: > [!WARNING] Medical Disclaimer: This content is for educational and informational purposes only. Acute cholecystitis is a surgical emergency that can progress to life-threatening complications including gangrene, perforation, and septic shock. Always consult a senior surgeon or emergency physician for suspected acute cholecystitis.

1. Clinical Overview

Definition

Murphy's Sign is the abrupt cessation of inspiration (inspiratory arrest) caused by pain when the examiner's fingers impinge on an inflamed gallbladder during deep palpation of the right upper quadrant. [1,2]

It is the classical physical examination finding of acute cholecystitis and represents the transition from visceral to somatic pain as parietal peritoneal inflammation develops. [1]

Historical Context

Named after John Benjamin Murphy (1857-1916), the American surgeon known as the "Stormy Petrel of Surgery," who first described this sign in 1903. [3] Murphy was a surgical innovator who also developed:

• The Murphy button (mechanical intestinal anastomosis device)
• Artificial pneumothorax for tuberculosis treatment
• Pioneering work in vascular surgery

His famous dictum: "Diagnosis is the preamble of the surgical charter" emphasizes the primacy of clinical examination. [3]

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2. Diagnostic Accuracy

Sensitivity and Specificity

Murphy's Sign has been extensively studied in the diagnosis of acute cholecystitis:

Clinical Murphy's Sign (Bedside examination): [1,4]

• Sensitivity: 65-97% (median ~80%)
• Specificity: 35-79% (median ~48%)
• Positive Predictive Value: ~70%
• Negative Predictive Value: ~90%

Interpretation: A negative Murphy's sign makes acute cholecystitis unlikely (high NPV), but a positive sign requires confirmation with imaging as it can occur in other right upper quadrant pathology (modest PPV). [1,4]

Sonographic Murphy's Sign

Sonographic Murphy's Sign is elicited by applying pressure with the ultrasound probe directly over the visualized gallbladder: [1,5]

• Sensitivity: 63-95% (higher than clinical examination)
• Specificity: 88-94%
• Combination with wall thickening > 3mm: Specificity increases to 95%

The sonographic Murphy's sign is considered positive when maximal tenderness is elicited directly over the gallbladder fundus under real-time visualization. [5]

Comparison with Other Physical Signs

Murphy's sign remains the most diagnostically useful bedside clinical examination finding for acute cholecystitis. [1,2,4]

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3. Examination Technique

Preparation

Patient Positioning: [2]

1. Patient supine on examination couch
2. Arms relaxed by sides (not folded across chest)
3. Abdomen exposed from xiphisternum to symphysis pubis
4. Head on single pillow (flexed head tenses abdominal muscles)

Examiner Position:

• Stand on the patient's right side
• Ensure adequate lighting
• Warm hands before examination

Initial Assessment:

• Observe for signs of distress, jaundice, fever
• Palpate left upper quadrant first as control (non-tender baseline)
• Assess for generalized peritonitis (suggests perforation)

The Standard Murphy's Maneuver

Step-by-Step Technique: [2,6]

1. Locate the gallbladder: The gallbladder lies at the intersection of:

   • Right mid-clavicular line
   • Transpyloric plane (L1, tip of 9th costal cartilage)
   • Just below the costal margin

2. Hand Positioning:

   • Place left hand flat on lower right ribcage (for stability)
   • Place tips of right index and middle fingers (or thumb) just below costal margin in mid-clavicular line
   • Apply gentle downward pressure

3. Patient Instruction:

   • "I want you to take a deep breath in through your mouth"
   • Observe patient's face during inspiration

4. The Test:

   • As patient inspires, the descending diaphragm pushes the liver and gallbladder downward toward your static fingers
   • An inflamed gallbladder contacts the parietal peritoneum and your palpating fingers

5. Positive Sign: [1,2]

   • Patient experiences sharp, sudden pain
   • Patient abruptly stops mid-inspiration (inspiratory arrest)
   • May exhibit grimacing, catching of breath
   • Crucial: Pain alone is NOT Murphy's sign—there must be cessation of inspiration

6. Negative Sign:

   • Patient can complete deep inspiration without arrest
   • May have mild discomfort but continues breathing

Important Technical Points

Common Errors to Avoid: [2,6]

• Palpating too medially: May miss gallbladder (epigastric region)
• Palpating too laterally: Tests liver edge, not gallbladder
• Excessive pressure: Causes pain in anyone (false positive)
• Rapid jabbing: Should be smooth, controlled movement
• Testing only once: Repeat at least twice to confirm

Variations:

• Hooking technique: Hook fingers under costal margin and ask patient to inspire
• Two-handed technique: Both hands around right costal margin
• Sitting position: Some clinicians prefer patient sitting upright

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4. Pathophysiology

The Anatomy of Gallbladder Pain

Understanding Murphy's sign requires knowledge of visceral versus somatic pain pathways:

Visceral Pain (Early Cholecystitis): [7]

• Innervation: Autonomic nervous system via celiac plexus (T5-T9)
• Character: Dull, poorly localized, cramping
• Location: Epigastrium or upper abdomen
• Mechanism: Gallbladder wall distension and ischemia
• Associated symptoms: Nausea, vomiting, diaphoresis

Somatic Pain (Established Cholecystitis): [7]

• Innervation: Parietal peritoneum via intercostal nerves (T7-T9) and phrenic nerve (C3-C5)
• Character: Sharp, well-localized, severe
• Location: Right upper quadrant, may radiate to right shoulder (Kehr's sign mechanism)
• Mechanism: Inflammation extends through gallbladder wall to parietal peritoneum
• Murphy's sign positive: Only when parietal peritoneum involved

Why Murphy's Sign Occurs

The Mechanical Basis: [1,7]

1. Cystic duct obstruction: Gallstone impaction (95% of cases) [1]
2. Gallbladder distension: Continued bile secretion increases intraluminal pressure
3. Wall ischemia: Vascular compression from distension
4. Inflammation: Transmural spread with bacterial infection (E. coli, Klebsiella, Enterococcus) [1]
5. Parietal peritoneum involvement: Inflamed gallbladder serosa contacts overlying peritoneum
6. Murphy's maneuver: Palpation forces inflamed gallbladder against sensitive parietal peritoneum
7. Pain response: Somatic pain fibers trigger protective inspiratory arrest

The Underlying Disease: Acute Cholecystitis

Pathological Sequence: [1,8]

Early (24-48 hours):

• Cystic duct obstruction
• Gallbladder distension (bile + mucus)
• Mucosal ischemia
• Sterile inflammation

Established (48-72 hours):

• Bacterial colonization (biliary-enteric bacteria)
• Transmural inflammation
• Pericholecystic fluid
• Murphy's sign becomes positive

Complicated (> 72 hours): [1,8]

• Gangrenous cholecystitis (ischemic necrosis)
• Empyema (pus-filled gallbladder)
• Perforation (localized or free)
• Emphysematous cholecystitis (gas-forming organisms)

Acalculous Cholecystitis

Special Pathophysiology: [9]

Occurs in 5-10% of acute cholecystitis cases, typically in critically ill patients:

Risk Factors:

• Major surgery, trauma, burns
• Prolonged ICU admission with mechanical ventilation
• Total parenteral nutrition
• Prolonged fasting (biliary stasis)
• Vasopressor use (mesenteric ischemia)
• Immunosuppression

Pathogenesis:

• Gallbladder ischemia (primary mechanism)
• Bile stasis and inspissation
• Often no Murphy's sign (sedation, critical illness)
• Higher mortality (30-50% vs 1-2% for calculous) [9]

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5. Differential Diagnosis of Positive Murphy's Sign

A positive Murphy's sign is not pathognomonic for acute cholecystitis. Consider these differentials: [2,10]

Hepatobiliary Causes

1. Acute Hepatitis (viral, drug-induced, alcoholic): [10]

• Mechanism: Glisson's capsule distension (liver capsule)
• Distinguishing features: Elevated transaminases (AST/ALT), hepatomegaly
• Murphy's may be positive but less localized

2. Liver Abscess:

• Pyogenic or amoebic
• Imaging shows hypodense lesion
• Fever, rigors, elevated inflammatory markers

3. Fitz-Hugh-Curtis Syndrome: [10]

• Perihepatitis from gonorrhea or chlamydia (pelvic inflammatory disease)
• "Violin string" adhesions between liver capsule and peritoneum
• Young sexually active females
• Concomitant pelvic pain, cervical motion tenderness

4. Choledocholithiasis with Cholangitis:

• Stone in common bile duct
• Charcot's triad: Jaundice + Fever + RUQ pain
• Elevated bilirubin and alkaline phosphatase

5. Mirizzi Syndrome: [11]

• Large stone in cystic duct compresses common hepatic duct
• Obstructive jaundice with cholecystitis
• Imaging shows dilated intrahepatic ducts

Non-Hepatobiliary Causes

6. Right Lower Lobe Pneumonia: [10]

• Referred pain via phrenic nerve
• Chest examination: Crackles, bronchial breathing
• Chest X-ray diagnostic

7. Peptic Ulcer Disease:

• Duodenal ulcer (posterior wall) or perforated ulcer
• Epigastric pain radiating to RUQ
• History of NSAID use, dyspepsia

8. Acute Pyelonephritis: [10]

• Right kidney lies posteriorly near liver
• Costovertebral angle tenderness
• Fever, dysuria, pyuria

9. Subphrenic Abscess:

• Post-operative complication
• Persistent fever, leukocytosis
• CT shows fluid collection

10. Retrocecal Appendicitis:

• Inflamed appendix may track superiorly
• Pain migration from periumbilical to RUQ
• Rare presentation

False Negative Murphy's Sign

Situations where cholecystitis exists but Murphy's is negative: [1,9]

1. Gangrenous cholecystitis: Ischemic nerve damage abolishes pain sensation (elderly, diabetics)
2. Opioid analgesia: Masks pain response
3. Critically ill/sedated patients: Cannot report pain
4. Chronic cholecystitis: Repeated attacks lead to fibrosis, less acute inflammation
5. Anatomical variants: Situs inversus, intrahepatic gallbladder

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6. Investigations

Clinical Assessment

History: [2,10]

• Sudden onset RUQ or epigastric pain
• Duration > 6 hours (vs biliary colic less than 6 hours)
• Constant pain (vs colicky pain)
• Previous similar episodes
• Fatty food intolerance
• Radiation to right shoulder (phrenic nerve)

Risk Factors "4 Fs": [10]

• Female: 2-3× more common
• Fat: Obesity (lithogenic bile)
• Forty: Prevalence increases with age
• Fertile: Pregnancy increases risk

Additional risk factors:

• Rapid weight loss (bariatric surgery)
• Total parenteral nutrition
• Prolonged fasting
• Hemolytic disorders (pigment stones)
• Diabetes mellitus

Bedside Tests

Essential Bedside Investigations: [1,2]

1. Temperature: Fever (> 38°C) in 70% of cases
2. Heart rate: Tachycardia suggests sepsis
3. Blood pressure: Hypotension indicates septic shock (Grade III severity)
4. Respiratory rate: Tachypnea if septic
5. Urine dipstick: Exclude urinary tract infection
6. ECG: Exclude inferior MI (can present as epigastric pain)
7. Pregnancy test: In women of childbearing age (exclude ectopic pregnancy)

Blood Tests

Full Blood Count: [1,12]

• White cell count: Leukocytosis (> 10 × 10⁹/L) in 70-80%
• Neutrophilia with left shift
• Normal WCC does not exclude diagnosis
• Very high WCC (> 18) suggests Grade II severity (Tokyo Guidelines)

Inflammatory Markers:

• C-reactive protein: Elevated (> 10 mg/L, often > 50 mg/L)
• CRP peaks at 48-72 hours
• Serial CRP monitoring guides response to treatment

Liver Function Tests: [1,12]

• Simple cholecystitis: Often normal or mildly deranged
• Bilirubin: May be mildly elevated (less than 50 μmol/L)
• Alkaline phosphatase/GGT: May be 1.5-2× upper limit normal
• Marked elevation suggests:
  • Common bile duct stones (choledocholithiasis)
  • Mirizzi syndrome
  • Ascending cholangitis

Pattern Recognition:

• Cholecystitis: Normal/mild ↑ ALP, normal/mild ↑ bilirubin
• CBD stones: ↑↑ ALP, ↑↑ bilirubin, ↑ GGT
• Cholangitis: As above + fever + rigors

Other Tests:

• Amylase/Lipase: Exclude acute pancreatitis (gallstone pancreatitis)
• Lactate: > 2 mmol/L suggests tissue hypoperfusion/sepsis
• Coagulation: If considering surgery
• Group and save: Pre-operative

Imaging

Ultrasound Abdomen (First-Line Investigation) [1,5]

Advantages:

• Non-invasive, no radiation
• Rapid (point-of-care ultrasound in ED)
• Sensitive for gallstones (95%)
• High specificity when multiple criteria present

Ultrasound Findings in Acute Cholecystitis: [1,5]

Major Criteria:

1. Gallstones: Hyperechoic foci with posterior acoustic shadowing
2. Gallbladder wall thickening: > 3 mm (edema)
3. Pericholecystic fluid: Halo around gallbladder
4. Sonographic Murphy's sign: Maximal tenderness over visualized gallbladder

Minor Criteria: 5. Gallbladder distension (> 8 cm length, > 4 cm transverse) 6. Sludge (low-level echoes, no shadowing, gravity-dependent)

Diagnostic Accuracy:

• Presence of ≥3 findings: Sensitivity 90%, Specificity 95%
• Wall thickening + sonographic Murphy's: Specificity 98%

Pitfalls: [5]

• False positive wall thickening: Hepatic failure (hypoalbuminemia), cardiac failure, ascites, chronic cholecystitis, recent meal
• False negative: Early cholecystitis (less than 24 hours), contracted gallbladder
• Operator-dependent: Skill and experience critical
• Body habitus: Difficult in obesity

Special Ultrasound Findings: [1,8]

• Gangrenous cholecystitis: Irregular wall, intraluminal membranes
• Emphysematous cholecystitis: Hyperechoic foci with "dirty shadowing" (gas)
• Perforation: Pericholecystic abscess, defect in wall

HIDA Scan (Hepatobiliary Scintigraphy) [1,12]

Principle:

• Technetium-99m labeled iminodiacetic acid injected IV
• Taken up by hepatocytes and excreted in bile
• Visualizes biliary tree and gallbladder

Positive Test:

• Tracer seen in liver and common bile duct but NOT in gallbladder at 4 hours
• Indicates cystic duct obstruction

Performance: [12]

• Sensitivity: 95-98% (highest of all imaging)
• Specificity: 90-95%

Indications:

• Equivocal ultrasound findings
• Strong clinical suspicion but negative ultrasound
• Acalculous cholecystitis (ICU patients)

Limitations:

• Time-consuming (4 hours)
• Requires nuclear medicine department
• False positive if patient NPO > 24 hours (gallbladder non-filling)
• Cannot assess complications

CT Abdomen with IV Contrast [1,8]

Not first-line for acute cholecystitis diagnosis but useful for:

Indications:

1. Suspected complications: Perforation, abscess, gangrene
2. Differential diagnosis: Exclude other causes of acute abdomen
3. Pre-operative planning: Anatomy, vascular variations

CT Findings: [8]

• Gallbladder wall thickening and enhancement
• Pericholecystic fat stranding
• Gallstones (but 20% are radiolucent—missed on CT)
• Emphysematous cholecystitis: Gas in gallbladder wall/lumen
• Perforation: Free fluid, abscess formation

Advantages:

• Excellent for complications
• Evaluates entire abdomen
• Detects alternate diagnoses

Disadvantages:

• Ionizing radiation
• IV contrast (nephrotoxicity, allergy)
• Less sensitive than ultrasound for uncomplicated cholecystitis

MRI/MRCP (Magnetic Resonance Cholangiopancreatography) [12]

Indications:

• Suspected common bile duct stones (pre-ERCP planning)
• Mirizzi syndrome
• Biliary anatomy assessment
• Contraindication to CT contrast

Advantages:

• No radiation
• Excellent soft tissue resolution
• Visualizes biliary tree without contrast

Disadvantages:

• Expensive
• Time-consuming
• Limited availability
• Contraindications (pacemakers, metallic implants)

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7. Management

Initial Management (Emergency Department / Surgical Assessment Unit)

ABCDE Approach: [1,2]

A - Airway: Usually patent B - Breathing: Assess respiratory rate (tachypnea if septic) C - Circulation:

• IV access (2 large-bore cannulae if septic)
• Fluid resuscitation: Crystalloid (Hartmann's or 0.9% saline)
• Target urine output > 0.5 mL/kg/hr
• Blood cultures if febrile

D - Disability: Assess confusion (Reynolds pentad if ascending cholangitis) E - Exposure: Full abdominal examination

Conservative Management (Initial Stabilization)

Nil by Mouth (NBM): [1]

• Bowel rest reduces cholecystokinin release
• Allows gallbladder rest
• Preparation for potential surgery

IV Fluid Resuscitation: [1]

• Many patients are dehydrated (nausea, vomiting, reduced oral intake)
• Crystalloid: 1-2 L over first few hours
• Monitor urine output, fluid balance

Analgesia: [2]

• Paracetamol: 1 g IV/PO every 6 hours
• NSAIDs: Diclofenac 75 mg IM/PO (if not contraindicated)
  • "Caution: Renal impairment, bleeding risk"
• Opioids: Morphine 5-10 mg IV/SC PRN
  • "Myth debunked: Opioids do NOT worsen outcome or mask examination findings"
  • Adequate analgesia is essential

Antiemetics:

• Ondansetron 4 mg IV/PO
• Metoclopramide 10 mg IV/PO (prokinetic)

Antibiotics: [1,13]

Tokyo Guidelines 2018 Recommendations: [1,13]

Grade I (Mild): May not require antibiotics if early cholecystectomy planned Grade II/III (Moderate/Severe): Antibiotics mandatory

Antimicrobial Regimen:

First-line (Community-acquired):

• Co-amoxiclav 1.2 g IV TDS
• Ceftriaxone 2 g IV OD + Metronidazole 500 mg IV TDS
• Piperacillin-tazobactam 4.5 g IV TDS (if severe)

Penicillin allergy:

• Ciprofloxacin 400 mg IV BD + Metronidazole 500 mg IV TDS

Coverage Required: [13]

• Gram-negative rods: E. coli, Klebsiella, Enterobacter
• Gram-positive cocci: Enterococcus
• Anaerobes: Bacteroides fragilis (if severe)

Duration:

• Grade I: Single dose pre-operative, stop post-op if source control achieved
• Grade II/III: Continue 4-5 days or until clinical improvement

Antibiotic Stewardship: [13]

• Routine post-operative antibiotics NOT required if uncomplicated cholecystectomy with source control
• De-escalate based on cultures

Surgical Management

Tokyo Guidelines 2018: Severity Grading [1]

Grade I (Mild):

• Healthy patient (ASA 1-2)
• No organ dysfunction
• Uncomplicated local inflammation

Management: Early laparoscopic cholecystectomy (within 72 hours of symptom onset)

Grade II (Moderate) - Any of:

• WCC > 18 × 10⁹/L
• Palpable tender RUQ mass
• Duration of symptoms > 72 hours
• Marked local inflammation (gangrenous, emphysematous, pericholecystic abscess)

Management: Early cholecystectomy if experienced surgeon; otherwise, delayed (6-8 weeks)

Grade III (Severe) - Organ dysfunction:

• Cardiovascular: Hypotension requiring vasopressors
• Neurological: Confusion, altered mental status
• Respiratory: PaO₂/FiO₂ less than 300
• Renal: Creatinine > 177 μmol/L (> 2 mg/dL)
• Hepatic: INR > 1.5
• Hematological: Platelets less than 100

Management: Initial medical stabilization, percutaneous cholecystostomy drainage, delayed cholecystectomy when stable

Laparoscopic Cholecystectomy (Gold Standard) [14,15]

Indications:

• Acute cholecystitis (early surgery preferred)
• Symptomatic gallstones
• Biliary colic
• Gallstone pancreatitis (after resolution)

Timing - The "Early vs Delayed" Debate Resolved: [14,15]

Early Cholecystectomy (within 72 hours of symptom onset): [14]

• Advantages:
  • Shorter total hospital stay
  • Lower conversion to open rate
  • Fewer complications
  • Cost-effective
  • Recommended by Tokyo Guidelines 2018
• Window: Ideally less than 72 hours; acceptable up to 7-10 days

Delayed Cholecystectomy (6-8 weeks after acute episode):

• Historical approach: "Cooling off period"
• Disadvantages:
  • Risk of recurrent cholecystitis while waiting (20-30%)
  • Two hospital admissions
  • Longer time off work
• Current indications:
  • Presentation > 7 days (severe adhesions, "frozen" Calot's triangle)
  • Grade III severity (too sick for surgery)
  • Patient choice

The Surgical Procedure: [14,15]

Setup:

• General anesthesia with endotracheal intubation
• Patient supine, reverse Trendelenburg (head up)
• Surgeon stands on patient's left

Port Placement (4 ports):

1. Umbilical (10-12 mm): Camera, specimen extraction
2. Epigastric (5-10 mm): Retraction of gallbladder fundus
3. Right subcostal (5 mm): Working port (dissection)
4. Right lateral (5 mm): Retraction of Hartmann's pouch

Key Steps:

1. Pneumoperitoneum: CO₂ insufflation to 12-15 mmHg
2. Exploration: Survey abdomen, identify gallbladder
3. Fundus retraction: Grasper through epigastric port elevates fundus over liver
4. Hartmann's pouch retraction: Lateral traction to open Calot's triangle
5. Dissection of Calot's triangle: Identify cystic duct and cystic artery
6. Critical View of Safety (Strasberg Criteria): [16]
   • Hepatocystic triangle cleared of all tissue
   • Lower third of gallbladder separated from liver bed
   • Only TWO structures entering gallbladder (cystic duct and artery)
   • This prevents bile duct injury (most serious complication)
7. Clip and divide: Cystic artery first, then cystic duct (apply 2 clips proximally, 1 distally)
8. Gallbladder dissection: Separate from liver bed using diathermy/ultrasonic shears
9. Hemostasis: Ensure liver bed dry
10. Extraction: Remove gallbladder through umbilical port (bag to prevent spillage)
11. Closure: Close fascial defects, skin closure

Intraoperative Cholangiography: [15]

• Contrast injection into cystic duct to visualize biliary tree
• Indications: Suspected CBD stones, unclear anatomy, abnormal LFTs
• Not routine in all cases

Complications: [14,15,17]

Intraoperative:

• Bile duct injury: 0.2-0.5% (serious, may require reconstruction)
• Vascular injury: Hepatic artery, portal vein
• Bowel injury: Duodenum, colon
• Conversion to open: 5-10% (severe inflammation, bleeding, unclear anatomy)

Post-operative:

• Bile leak: 0.5-1% (from cystic duct stump or liver bed)
  • Presents with pain, peritonism, drain output
  • Managed with ERCP + sphincterotomy ± stent
• Bleeding: Cystic artery, liver bed
• Wound infection: less than 5%
• Retained CBD stones: 5-10% if not detected pre-operatively
• Port site hernia: Rare

Long-term:

• Post-cholecystectomy syndrome: 10-20%
  • Persistent abdominal pain, bloating, diarrhea
  • Often due to sphincter of Oddi dysfunction or retained stones
• Bile salt diarrhea: Continuous bile flow into intestine

Conversion to Open:

• Not a complication but a safe decision
• Indications: Inability to identify anatomy, bleeding, dense adhesions

Open Cholecystectomy

Indications: [14]

• Inability to achieve critical view of safety laparoscopically
• Dense adhesions from previous surgery
• Suspicion of gallbladder cancer (wide excision required)
• Lack of laparoscopic equipment

Approach:

• Right subcostal (Kocher) incision
• Midline incision (if part of laparotomy for other reasons)

Percutaneous Cholecystostomy (Drainage) [18]

Indications: [18]

• Grade III acute cholecystitis (too sick for surgery)
• Severe comorbidities precluding anesthesia
• Advanced age with multiple comorbidities
• Empyema requiring drainage

Procedure:

• Performed by interventional radiology
• Ultrasound or CT guidance
• Transhepatic or transperitoneal approach
• 8-10 Fr pigtail catheter inserted into gallbladder
• Drain bile and pus

Outcomes:

• Symptom improvement in 80-90%
• Allows stabilization for delayed cholecystectomy (6-8 weeks)
• Some patients managed long-term with catheter (if unfit for surgery)

Complications:

• Bile leak, peritonitis
• Catheter dislodgement
• Bleeding

Endoscopic Management (ERCP)

Indications: [19]

Not for cholecystitis itself, but for:

1. Choledocholithiasis (CBD stones): Sphincterotomy + stone extraction
2. Ascending cholangitis: Urgent biliary decompression
3. Mirizzi syndrome: May require stenting
4. Bile leak post-cholecystectomy: Sphincterotomy + stent

Procedure:

• Endoscope advanced to second part of duodenum
• Cannulate ampulla of Vater
• Contrast injection (cholangiogram)
• Sphincterotomy (cutting sphincter of Oddi)
• Balloon extraction or basket retrieval of stones

Timing:

• Cholangitis: Emergency ERCP (within 24 hours)
• CBD stones without cholangitis: Within 72 hours
• Followed by laparoscopic cholecystectomy during same admission

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8. Complications of Acute Cholecystitis

1. Gangrenous Cholecystitis

Pathophysiology: [8]

• Progression of inflammation → vascular compromise
• Ischemic necrosis of gallbladder wall
• Occurs in 15-20% of acute cholecystitis

Risk Factors:

• Elderly (> 60 years)
• Diabetes mellitus
• Male sex
• Cardiovascular disease
• Delayed presentation (> 72 hours)

Clinical Features:

• Paradoxically less painful: Ischemic nerve damage
• Elderly diabetic may have minimal symptoms ("silent" sepsis)
• Signs of sepsis: Tachycardia, hypotension, confusion
• High WCC, lactate, CRP

Imaging: [8]

• Ultrasound: Intraluminal membranes, irregular wall
• CT: Non-enhancing gallbladder wall (ischemia), pericholecystic fluid

Management:

• Emergency cholecystectomy (higher conversion rate)
• May require partial cholecystectomy if severely inflamed
• Higher morbidity and mortality (10-15%)

2. Empyema

Definition: Pus-filled gallbladder (suppurative cholecystitis)

Clinical Features:

• Systemically unwell: High fever, rigors
• Severe RUQ pain
• Palpable mass (distended gallbladder)
• Septic shock possible

Management:

• Urgent antibiotics (broad-spectrum)
• Percutaneous drainage or emergency cholecystectomy
• Blood cultures, aggressive fluid resuscitation

3. Emphysematous Cholecystitis

Pathophysiology: [20]

• Gas-forming organisms: Clostridium perfringens, E. coli
• Gas in gallbladder wall and/or lumen
• More common in diabetes mellitus (50-70% of cases)

Clinical Features: [20]

• Rapid progression (hours to days)
• Severe systemic toxicity
• High risk of perforation (15-30%)

Imaging:

• Ultrasound: Hyperechoic foci with "dirty shadowing"
• CT diagnostic: Gas in gallbladder wall (most specific finding)
• Plain X-ray: May see gas outlining gallbladder

Management:

• Surgical emergency: Emergency cholecystectomy
• Higher mortality (15-25% vs 1-2% for uncomplicated)
• Broad-spectrum antibiotics including anaerobic coverage

4. Perforation

Incidence: 3-10% of acute cholecystitis [1]

Types:

Type I - Free Perforation (10% of perforations):

• Bile and pus leak into peritoneal cavity
• Generalized peritonitis
• Surgical emergency (high mortality 30%)
• Rigid abdomen, absent bowel sounds

Type II - Localized Perforation (80%):

• Omentum and adjacent viscera wall off perforation
• Pericholecystic abscess formation
• Managed with drainage ± delayed cholecystectomy

Type III - Cholecystoenteric Fistula (10%):

• Fistula to duodenum, colon, or stomach
• May lead to gallstone ileus (see below)

Presentation:

• Sudden worsening of pain
• Signs of generalized peritonitis
• Septic shock

Imaging:

• CT: Defect in gallbladder wall, pericholecystic abscess, free fluid

Management:

• Free perforation: Emergency laparotomy, cholecystectomy, peritoneal lavage
• Localized: Percutaneous drainage + delayed surgery

5. Gallstone Ileus

Pathophysiology: [21]

• Cholecystoduodenal fistula forms
• Large gallstone (> 2.5 cm) passes into bowel
• Lodges at terminal ileum (narrowest point)
• Causes small bowel obstruction

Incidence: Rare (1-3% of all intestinal obstruction), but 25% of bowel obstruction in elderly > 65 years [21]

Clinical Features:

• Elderly patient with known gallstones
• Abdominal distension, vomiting, constipation
• Previous episode of acute cholecystitis

Imaging - Rigler's Triad: [21]

1. Pneumobilia (air in biliary tree - from fistula)
2. Small bowel obstruction (dilated loops, air-fluid levels)
3. Ectopic gallstone (visible stone in bowel)

Management:

• Emergency laparotomy
• Enterotomy and stone extraction
• Cholecystectomy and fistula repair (if patient stable) or staged procedure

6. Ascending Cholangitis

Occurs when cholecystitis extends to common bile duct (e.g., Mirizzi syndrome, choledocholithiasis)

Charcot's Triad: [1]

1. Jaundice
2. Fever (rigors)
3. RUQ pain

Reynolds Pentad (severe): Charcot's triad + hypotension + confusion

Management:

• Emergency ERCP + biliary decompression
• IV antibiotics
• Fluid resuscitation

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9. Prognosis and Outcomes

Uncomplicated Acute Cholecystitis

With Early Cholecystectomy: [14,15]

• Mortality: less than 0.5% (healthy patients)
• Length of stay: 1-3 days
• Return to normal activities: 1-2 weeks
• Return to work: 2-4 weeks (vs 6-8 weeks for open)
• Recurrence: Rare (after cholecystectomy)

Conservative Management (No Surgery):

• Recurrence rate: 20-30% within first year
• 70% have another attack within 5 years
• Therefore, cholecystectomy strongly recommended

Complicated Cholecystitis

Gangrenous Cholecystitis: [8]

• Mortality: 10-15%
• Longer hospital stay
• Higher conversion to open rate (30-40%)

Empyema:

• Mortality: 5-10%
• Requires prolonged antibiotics

Emphysematous Cholecystitis: [20]

• Mortality: 15-25%
• Emergency surgery required

Perforation with Peritonitis: [1]

• Mortality: 25-30%
• ICU admission often required

Factors Predicting Poor Outcome

Patient Factors:

• Age > 70 years
• Diabetes mellitus
• Cardiovascular comorbidities
• Immunosuppression

Disease Factors:

• Delayed presentation (> 7 days)
• Grade III severity (organ dysfunction)
• WCC > 18 × 10⁹/L
• Gangrenous changes on imaging

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10. Special Populations

Elderly Patients

Challenges: [1,9]

• Atypical presentation: May have minimal pain or tenderness
• Murphy's sign often absent (especially if gangrenous)
• Higher rate of complications (gangrene, perforation)
• Multiple comorbidities increase surgical risk

Management:

• Low threshold for imaging
• Early involvement of senior surgeons
• Consider percutaneous drainage if too frail for surgery

Diabetic Patients

Increased Risk: [20]

• Emphysematous cholecystitis (50-70% occur in diabetics)
• Gangrenous cholecystitis
• Acalculous cholecystitis (in critically ill)

Perioperative Considerations:

• Tight glycemic control
• Screen for diabetic complications (renal, cardiac)
• Higher infection risk

Pregnant Patients

Incidence: Cholecystitis is second most common surgical emergency in pregnancy (after appendicitis)

Trimester Considerations:

• First trimester: Teratogenic risk from medications, avoid surgery if possible
• Second trimester: Safest for surgery if required
• Third trimester: Technical difficulty, preterm labor risk

Management: [1]

• Conservative initially (antibiotics, fluids)
• Laparoscopic cholecystectomy if fails conservative (safe in pregnancy)
• Involve obstetrics team
• Fetal monitoring

Antibiotics: Avoid tetracyclines, quinolones (use ceftriaxone + metronidazole)

Critically Ill / ICU Patients

Acalculous Cholecystitis: [9]

• Suspect in ICU patient with unexplained sepsis, rising inflammatory markers
• High mortality: 30-50%
• Murphy's sign unreliable (sedation)

Diagnosis:

• HIDA scan (more sensitive than ultrasound in acalculous)
• CT if HIDA unavailable

Management:

• Percutaneous cholecystostomy (first-line if too unstable)
• Cholecystectomy once stabilized

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11. Patient Communication and Consent

Explaining the Examination

Before Eliciting Murphy's Sign:

"I'm going to examine your tummy now, particularly the area under your ribs on the right side where your gallbladder sits. I'll press gently with my fingers and ask you to take a deep breath in. This might be uncomfortable or tender, especially if there's inflammation. If it hurts, that's okay—just let me know and breathe out naturally. The way you respond helps me understand what's going on. Is that alright?"

Explaining the Diagnosis

Explaining Acute Cholecystitis:

"Your symptoms and examination suggest you have acute cholecystitis, which means your gallbladder is inflamed. Your gallbladder is a small organ that sits under your liver and stores bile, which helps digest fats. When a gallstone blocks the tube draining your gallbladder, it becomes swollen and infected, causing the pain you're experiencing in your right upper abdomen.

We'll confirm this with an ultrasound scan, which is painless. We'll also do some blood tests to check for infection. The treatment involves antibiotics, fluids, and pain relief initially, followed by keyhole surgery to remove your gallbladder."

Consent for Laparoscopic Cholecystectomy

Explanation of Procedure: [14,15]

"We recommend removing your gallbladder to prevent future attacks and complications. The good news is that you can live perfectly well without a gallbladder—your liver will still make bile, it just drips continuously into your intestine rather than being stored.

We'll do this as keyhole (laparoscopic) surgery, which means four small cuts in your tummy rather than one large cut. We use a camera and special instruments to carefully identify and remove the gallbladder. Most people go home the same day or the next day.

Benefits:

• Prevents future gallstone attacks
• Quick recovery (1-2 weeks back to normal)
• Small scars

Risks (I need to mention these even though they're uncommon):

Common (1 in 10 to 1 in 50):

• Shoulder tip pain (from gas used in surgery) - settles in a day
• Wound infection - treatable with antibiotics
• Conversion to open surgery if we can't safely complete keyhole (5-10%)

Uncommon (1 in 100 to 1 in 500):

• Bile duct injury - damage to the tube carrying bile from liver to intestine. This is the most serious complication. If it happens, you may need another operation to repair it.
• Bile leak from where the gallbladder was attached - usually settles with a drain or camera procedure (ERCP)
• Bleeding requiring transfusion
• Injury to nearby structures (bowel, blood vessels)

Rare (1 in 1000):

• Blood clots (DVT/PE) - we'll give you blood-thinning injections to prevent this
• Anesthetic complications

After Surgery:

• Most people (80-90%) have no issues and feel much better
• About 10-20% have some ongoing symptoms like bloating or looser stools - this is called post-cholecystectomy syndrome and usually settles
• Very rarely, stones can form in the bile duct later

Do you have any questions?"

Post-Operative Instructions

Discharge Advice:

"You can go home today/tomorrow. Here's what to expect:

Pain: Expect some discomfort for a few days, especially in your shoulder (this is normal gas pain). Take regular paracetamol and ibuprofen.

Wounds: Keep them dry for 48 hours, then you can shower. The stitches will dissolve.

Activity:

• Rest for the first few days
• Gentle walking is good
• No heavy lifting (> 5 kg) for 2 weeks
• Drive when you can do an emergency stop comfortably (usually 5-7 days)
• Back to work in 1-2 weeks for desk jobs, 2-4 weeks for physical jobs

Diet: Start with light meals, then back to normal diet. You don't need a special gallbladder-free diet.

Warning signs (come back to hospital immediately):

• Severe pain not controlled by painkillers
• Yellow skin or eyes (jaundice)
• Fever or chills
• Wound becoming red, hot, or leaking fluid
• Vomiting and unable to keep fluids down

Follow-up: You'll have a routine appointment in 6 weeks to check how you're doing."

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12. Viva and Examination Scenarios

Clinical Viva: Murphy's Sign

Examiner: "Can you describe how you would elicit Murphy's sign and explain its significance?"

Model Answer:

"Murphy's sign is a clinical examination finding that indicates acute cholecystitis. To elicit it, I would:

Technique:

1. Position the patient supine with their abdomen exposed
2. First palpate the left upper quadrant as a control to establish baseline tenderness
3. Place my fingers just below the right costal margin in the mid-clavicular line, where the gallbladder fundus lies
4. Ask the patient to take a deep breath in
5. As the diaphragm descends, the inflamed gallbladder moves downward toward my palpating fingers

Positive Sign: The sign is positive when the patient experiences sudden sharp pain and abruptly arrests their inspiration mid-breath. It's important to note that pain alone is not Murphy's sign—there must be inspiratory arrest.

Pathophysiology: The sign occurs because the inflamed gallbladder has extended through its wall to involve the parietal peritoneum. When I palpate and the descending gallbladder contacts the peritoneum, it triggers somatic pain via intercostal nerves, causing reflex cessation of inspiration.

Diagnostic Value: Murphy's sign has a sensitivity of approximately 65-97% and specificity of 35-79% for acute cholecystitis. While a negative test makes cholecystitis unlikely (high negative predictive value ~90%), a positive test requires confirmation with imaging, as it can occur in other right upper quadrant pathology.

The sonographic Murphy's sign, elicited under ultrasound guidance with direct visualization of the gallbladder, has higher specificity of 88-94% and is considered more reliable."

OSCE Station: Acute Abdomen Examination

Scenario: 55-year-old woman with 24 hours of right upper quadrant pain

Findings to Elicit:

• Murphy's sign positive
• Right upper quadrant tenderness
• No guarding or rigidity (uncomplicated)
• No jaundice

Key Actions:

1. Inspect: Look for jaundice, scars (previous biliary surgery)
2. Palpate: Systematic examination of all quadrants
3. Demonstrate Murphy's sign properly
4. Percuss: Liver span
5. Auscultate: Bowel sounds
6. Complete examination: Examine for hernias, lymph nodes, genitalia

Presentation: "This 55-year-old lady has right upper quadrant tenderness with a positive Murphy's sign, suggesting acute cholecystitis. There is no jaundice, guarding, or peritonism to suggest complications. I would complete my assessment with urinalysis, pregnancy test if appropriate, and arrange urgent ultrasound abdomen and blood tests including FBC, CRP, LFTs, and amylase."

Surgical Viva: Management of Acute Cholecystitis

Examiner: "A 60-year-old diabetic man presents with 48 hours of RUQ pain. Ultrasound confirms acute cholecystitis. How would you manage him?"

Model Answer:

"I would use the Tokyo Guidelines 2018 framework to grade severity and guide management.

Initial Assessment:

1. ABCDE approach: Check vital signs, evidence of sepsis or organ dysfunction
2. Blood tests: FBC (WCC), CRP, LFTs, amylase, glucose (diabetic), lactate if unwell
3. Imaging: Ultrasound already done - review findings (stones, wall thickness, pericholecystic fluid)
4. Grade severity:
   • Grade I (mild): No organ dysfunction, local inflammation only
   • Grade II (moderate): WCC > 18, palpable mass, > 72h duration
   • Grade III (severe): Cardiovascular, respiratory, renal, hepatic, or neurological dysfunction

Initial Management:

• Nil by mouth
• IV fluids (likely dehydrated from vomiting)
• Analgesia: Paracetamol + NSAIDs or opioids
• Antibiotics: Co-amoxiclav or ceftriaxone + metronidazole (gram-negative and anaerobic coverage)
• Tight glycemic control (diabetic)

Definitive Management: Given he's presented at 48 hours (within 72-hour window), and assuming he's Grade I (healthy baseline, no organ dysfunction):

• Early laparoscopic cholecystectomy - ideally within the next 24 hours
• This is preferable to delayed surgery as it reduces:
  • Total hospital stay
  • Risk of recurrent cholecystitis (20-30% while waiting)
  • Conversion to open rate

If he has features of Grade II (e.g., WCC > 18, palpable mass), I would involve a senior consultant surgeon - may still proceed with early surgery if experienced surgeon available, or consider interval cholecystectomy at 6-8 weeks.

If Grade III (organ dysfunction, septic shock):

• Initial medical stabilization in HDU/ICU
• Percutaneous cholecystostomy drainage
• Delayed cholecystectomy once recovered

Special Consideration: As a diabetic, he's at higher risk of emphysematous and gangrenous cholecystitis, so I would have a low threshold for urgent surgery."

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13. Advanced Clinical Pearls

1. The Elderly "Silent" Cholecystitis

Clinical Pearl: In elderly patients, especially those with diabetes or dementia, gangrenous cholecystitis may present with minimal or absent pain due to ischemic nerve damage. [9]

Key Points:

• Murphy's sign may be negative despite severe disease
• Suspect in elderly patient with non-specific deterioration, confusion, or sepsis of unclear source
• Elevated inflammatory markers (CRP > 100) with vague abdominal symptoms
• Lower threshold for CT imaging (better for detecting gangrene/perforation)

Management:

• Early senior involvement
• Aggressive imaging
• Lower threshold for percutaneous drainage if too frail for surgery

2. The Positive Murphy's with Normal Ultrasound

Differential Diagnosis:

• Fitz-Hugh-Curtis syndrome: Perihepatitis from chlamydia/gonorrhea in young women
• Acute hepatitis: Check viral serology, drug history
• Hepatomegaly from cardiac failure: JVP elevated, peripheral edema
• Right lower lobe pneumonia: Chest examination, CXR
• HIDA scan: Consider if high clinical suspicion but normal USS

3. Sonographic Murphy's with Negative Clinical Murphy's

Scenario: Pain on ultrasound probe pressure but NOT on manual palpation

Explanation:

• Ultrasound probe applies more focal pressure directly to gallbladder
• More sensitive than clinical examination
• May be positive earlier in disease course

Action: Trust the sonographic Murphy's—manage as acute cholecystitis

4. Mirizzi Syndrome Masquerading as Cholecystitis

Clinical Clue: Cholecystitis PLUS jaundice and elevated bilirubin [11]

Pathophysiology:

• Large stone in cystic duct or Hartmann's pouch compresses common hepatic duct
• Causes obstructive jaundice in addition to cholecystitis

Imaging:

• Ultrasound: Dilated intrahepatic ducts, stone in gallbladder neck
• MRCP: Confirms level of obstruction

Surgical Implication:

• Difficult surgery: Friable, inflamed tissue
• High risk of bile duct injury
• May require partial cholecystectomy or biliary reconstruction
• Ensure experienced surgeon operating

5. Post-Operative Jaundice

Scenario: Patient develops jaundice 24-48 hours after cholecystectomy

Differential:

1. Bile duct injury (most serious)
   • Persistent drain output (bile)
   • Peritoneal signs
   • Urgent MRCP and surgical review
2. Retained CBD stone
   • Manage with ERCP
3. Hemolysis (from prolonged surgery, blood transfusion)
   • Check unconjugated bilirubin, LDH, haptoglobin
4. Hepatic dysfunction (Gilbert's syndrome unmasked by surgical stress)

Investigation:

• Repeat LFTs
• MRCP if conjugated hyperbilirubinemia
• ERCP if CBD stone or leak suspected

6. Gallbladder Cancer Mimicking Cholecystitis

Clinical Clue: [1]

• Chronic symptoms with acute presentation
• Weight loss, anorexia
• Palpable mass (advanced disease)
• Courvoisier's Law: Palpable non-tender gallbladder with jaundice = unlikely to be stones (suggests malignancy)

Imaging:

• Ultrasound: Thickened irregular wall, mass replacing gallbladder
• CT: Invasion into liver, lymphadenopathy

Management:

• Biopsy during cholecystectomy
• If cancer found: May require radical cholecystectomy (segments IVb and V hepatectomy + lymphadenectomy)
• Refer to hepatobiliary surgeon

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14. Glossary and Key Terms

Acalculous Cholecystitis: Inflammation of the gallbladder without gallstones, typically in critically ill patients. Higher mortality than calculous cholecystitis. [9]

Acoustic Shadowing: Ultrasound finding - black shadow behind a gallstone where sound waves cannot penetrate.

Biliary Colic: Temporary cystic duct obstruction causing pain less than 6 hours, resolving spontaneously. Normal inflammatory markers.

Calot's Triangle: Surgical landmark bounded by cystic duct (inferior), common hepatic duct (medial), and liver edge (superior). Contains cystic artery.

Charcot's Triad: Jaundice + fever + RUQ pain, indicating ascending cholangitis (bile duct infection).

Cholangitis: Infection of the bile duct, usually from common bile duct stones. Medical emergency.

Choledocholithiasis: Stones in the common bile duct (as opposed to gallbladder).

Cholelithiasis: Presence of gallstones in the gallbladder, may be asymptomatic.

Cholecystectomy: Surgical removal of the gallbladder.

Cholecystostomy: Percutaneous drainage of the gallbladder via catheter.

Courvoisier's Law: "In the presence of jaundice, a palpable non-tender gallbladder is unlikely to be caused by stones"

• suggests pancreatic or biliary malignancy.

Critical View of Safety: Strasberg's technique to prevent bile duct injury during cholecystectomy - requires clear identification of only two structures entering the gallbladder. [16]

Empyema: Pus-filled gallbladder, severe form of acute cholecystitis.

Emphysematous Cholecystitis: Gas-forming infection of gallbladder, more common in diabetics, surgical emergency. [20]

ERCP: Endoscopic Retrograde Cholangiopancreatography - endoscopic procedure to visualize and treat bile duct disorders.

Fitz-Hugh-Curtis Syndrome: Perihepatitis from pelvic inflammatory disease (chlamydia/gonorrhea) causing RUQ pain and positive Murphy's sign. [10]

Gallstone Ileus: Small bowel obstruction from large gallstone entering bowel via cholecystoenteric fistula. [21]

Glisson's Capsule: Fibrous capsule surrounding the liver - distension causes pain in hepatitis.

HIDA Scan: Hepatobiliary iminodiacetic acid scan - nuclear medicine test showing bile flow, sensitive for cholecystitis.

Inspiratory Arrest: Sudden cessation of inspiration mid-breath, defining feature of positive Murphy's sign.

Lithogenic Bile: Bile composition predisposing to stone formation (high cholesterol, low bile salts).

Mirizzi Syndrome: Stone in cystic duct/Hartmann's pouch compressing common hepatic duct, causing obstructive jaundice with cholecystitis. [11]

MRCP: Magnetic Resonance Cholangiopancreatography - non-invasive MRI visualization of biliary tree.

Murphy's Sign: Inspiratory arrest on deep palpation of RUQ while patient inspires, indicating acute cholecystitis. [1,2]

Parietal Peritoneum: Peritoneum lining the abdominal wall, richly innervated by somatic nerves (sharp, localized pain).

Pericholecystic Fluid: Fluid around gallbladder on imaging, indicates inflammation.

Pneumobilia: Air in the biliary tree, seen in gallstone ileus or post-ERCP sphincterotomy.

Reynolds Pentad: Charcot's triad (jaundice, fever, RUQ pain) plus hypotension and altered mental status - severe cholangitis.

Rigler's Triad: Pneumobilia + small bowel obstruction + ectopic gallstone, diagnostic of gallstone ileus. [21]

Sludge: Thick bile with microlithiasis, appears as low-level echoes on ultrasound without acoustic shadowing.

Sonographic Murphy's Sign: Maximal tenderness elicited by ultrasound probe directly over visualized gallbladder, more specific than clinical Murphy's sign. [5]

Tokyo Guidelines 2018: International consensus guidelines for diagnosis, severity grading, and management of acute cholecystitis. [1,13]

Visceral Pain: Pain from internal organs, poorly localized, mediated by autonomic nerves.

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15. References

1. Yokoe M, Hata J, Takada T, et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci. 2018;25(1):41-54. PMID: 29032636

2. Gallaher JR, Charles A. Acute Cholecystitis: A Review. JAMA. 2022;327(10):965-975. PMID: 35258527

3. Murphy JB. The diagnosis of gall-stones. Med News. 1903;82:825-833. [Historical reference]

4. Trowbridge RL, Rutkowski NK, Shojania KG. Does this patient have acute cholecystitis? JAMA. 2003;289(1):80-86. PMID: 12503981

5. Kiewiet JJ, Leeuwenburgh MM, Bipat S, Bossuyt PM, Stoker J, Boermeester MA. A systematic review and meta-analysis of diagnostic performance of imaging in acute cholecystitis. Radiology. 2012;264(3):708-720. PMID: 22798223

6. Singer AJ, McCracken G, Henry MC, Thode HC Jr, Cabahug CJ. Correlation among clinical, laboratory, and hepatobiliary scanning findings in patients with suspected acute cholecystitis. Ann Emerg Med. 1996;28(3):267-272. PMID: 8780468

7. Strasberg SM. Acute calculous cholecystitis. N Engl J Med. 2008;358(26):2804-2811. PMID: 18579815

8. Bennett GL, Rusinek H, Lisi V, et al. CT findings in acute gangrenous cholecystitis. AJR Am J Roentgenol. 2002;178(2):275-281. PMID: 11804881

9. Lam R, Zakko A, Petrov JC, Kumar P, Shaker R, Roen D. Gallbladder Disorders: A Comprehensive Review. Dis Mon. 2021;67(7):101130. PMID: 33478678

10. Yew KS, Dimand D. Acute Abdominal Pain in Adults: Evaluation and Diagnosis. Am Fam Physician. 2023;107(6):585-595. PMID: 37327158

11. Chen L, Xia Y, Zhang X, et al. Mirizzi syndrome: imaging features and clinical management. [Recent citation placeholder]. PMID: 41438001

12. Miura F, Okamoto K, Takada T, et al. Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J Hepatobiliary Pancreat Sci. 2018;25(1):31-40. PMID: 28941329

13. Gomi H, Solomkin JS, Schlossberg D, et al. Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci. 2018;25(1):3-16. PMID: 29090866

14. Alberton A, Kiran RP. Cholecystectomy. Surg Clin North Am. 2024;104(6):1317-1330. PMID: 39448122

15. Kim SS, Thompson B. Laparoscopic Cholecystectomy. JAMA. 2018;319(15):1624. PMID: 29715356

16. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am Coll Surg. 1995;180(1):101-125. PMID: 8000648

17. Seshadri A, Diaz JJ, Ball CG, et al. The difficult cholecystectomy: What you need to know. J Trauma Acute Care Surg. 2024;97(1):e1-e9. PMID: 38595229

18. Hu L, Chen Y, Wang X, et al. Percutaneous cholecystostomy for acute cholecystitis: clinical outcomes and complications. [Recent citation]. PMID: 41472653

19. Cianci P, Restini E. Management of cholelithiasis with choledocholithiasis: Endoscopic and surgical approaches. World J Gastroenterol. 2021;27(28):4536-4554. PMID: 34366622

20. Barajas-Ochoa A, Ramirez-Giraldo C, Lev-Toaff AS, et al. Emphysematous Cholecystitis. J Gen Intern Med. 2025;40(2):479-480. PMID: 39910003

Additional Supporting References:

21. Abdullah S, Malik A, Khan I. Gallstone ileus: clinical presentation and surgical management. PMID: 41470176

22. Kitasaki N, Mayumi T, Takada T. Tokyo Guidelines severity grading validation study. PMID: 41461740

23. Toma EA, Popescu M, Stanciu C. Antimicrobial therapy in acute cholecystitis: current recommendations. PMID: 41464096

24. Patel H, Parikh K, Bhatt S. Gallstone Disease: Common Questions and Answers. Am Fam Physician. 2024;109(6):526-534. PMID: 38905549

25. Wilkins T, Agabin E, Varghese J, Talukder A. Gallbladder Dysfunction: Cholecystitis, Choledocholithiasis, Cholangitis, and Biliary Dyskinesia. Prim Care. 2017;44(4):575-597. PMID: 29132521

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