Cholecystitis Tokyo guideline

Criteria	Findings
Clinical Criteria
Local signs of inflammation	- Murphy's sign
	- Right upper quadrant mass, pain, or tenderness
Systemic signs of inflammation	- Fever
	- Elevated C-reactive protein (CRP)
	- Elevated white blood cell count (WBC)
Imaging Findings
	- Gallbladder wall thickening (>4 mm)
	- Pericholecystic fluid
	- Gallbladder distention
	- Gallstones or sludge
	- Positive sonographic Murphy's sign

Severity Grade	Criteria	Management
Grade I (Mild)	- Does not meet criteria for Grade II or III - No organ dysfunction	- Conservative Treatment: - NPO (Nothing by mouth) - IV Fluids to maintain hydration and electrolyte balance - Analgesia: NSAIDs (e.g., ibuprofen 400-800 mg every 6-8 hours) or opioids (e.g., morphine 2-4 mg IV every 4-6 hours) - Antibiotics targeting common biliary pathogens (e.g., Ceftriaxone 1-2 g IV every 24 hours + Metronidazole 500 mg IV every 8 hours) - Elective Laparoscopic Cholecystectomy after inflammation subsides
Grade II (Moderate)	- Elevated WBC count (>18,000/mm³) - Palpable tender mass in RUQ - Duration of symptoms >72 hours - Marked local inflammation (e.g., gangrenous cholecystitis, pericholecystic abscess)	- Conservative Treatment: - Similar to Grade I but with closer monitoring - Early Laparoscopic Cholecystectomy: - Ideally within 72 hours of presentation, especially for cases with gangrenous or complicated cholecystitis
Grade III (Severe)	- Cardiovascular dysfunction (hypotension requiring treatment) - Neurological dysfunction (altered mental status) - Respiratory dysfunction (PaO2/FiO2 ratio <300) - Renal dysfunction (oliguria, creatinine >2.0 mg/dL) - Hepatic dysfunction (INR >1.5) - Hematological dysfunction (platelet count <100,000/mm³)	- ICU Admission: - Essential for organ support and close monitoring - Aggressive Conservative Treatment: - NPO, IV Fluids, Analgesia, Antibiotics (e.g., Piperacillin/Tazobactam 4.5 g IV every 8 hours or Carbapenem based on institutional protocols) - Organ support tailored to specific dysfunction (e.g., vasopressors for hypotension, mechanical ventilation for respiratory failure) - Percutaneous Cholecystostomy: - Consider for critically ill patients who cannot tolerate surgery - Delayed/Interval Laparoscopic Cholecystectomy: - Performed after stabilization of organ dysfunction and improvement of the inflammatory process

Order Antibiotics Form

Medication	Dose	Route	Frequency	Duration
Ceftriaxone	2 grams	IV	Once daily	Until further notice or 7 days
Metronidazole	500 mg	IV	Every 8 hours	Until further notice or 7 days

General Notes

Early LC: Refers to laparoscopic cholecystectomy ideally performed within 72 hours for Grade II and as soon as feasible for Grade III after meeting specific criteria.
Delayed/Elective LC: Cholecystectomy performed after the acute inflammation subsides, usually after several weeks.
GB Drainage: Placement of a drainage catheter into the gallbladder, either percutaneously or endoscopically, to relieve pressure and inflammation.
CCI: Charlson Comorbidity Index, a score assessing a patient's burden of co-existing medical conditions.
ASA-PS: American Society of Anesthesiologists Physical Status Classification, a score reflecting a patient's overall health before surgery.
Bail-out Procedures: Alternative procedures like conversion to open cholecystectomy or subtotal cholecystectomy, employed when LC becomes too difficult or risky.

Figure 1: Grade I (Mild) Acute Cholecystitis

Path 1 (λ): If the patient has low surgical risk (CCI ≤ 5 and/or ASA-PS ≤ 2), proceed directly to early laparoscopic cholecystectomy (LC).
Path 2 (µ): If the patient has higher surgical risk (CCI ≥ 6 and/or ASA-PS ≥ 3), begin with antibiotics and general supportive care. After initial improvement, proceed with early LC.

Figure 2: Grade II (Moderate) Acute Cholecystitis

Path 1 (α λ): If the patient has low surgical risk (CCI ≤ 5 and/or ASA-PS ≤ 2), antibiotics and supportive care are successful (α), AND advanced LC techniques are available, then proceed with urgent/early LC.
Path 2 (α µ): If the patient has higher surgical risk (CCI ≥ 6 and/or ASA-PS ≥ 3), antibiotics and supportive care are successful (α), but advanced LC techniques may not be available, proceed with delayed/elective LC.
Path 3 (ϕ λ/µ): If antibiotics and supportive care fail to control the inflammation (ϕ), regardless of surgical risk, urgent/early GB drainage is necessary.
- After drainage, if the patient has low surgical risk (λ), proceed with delayed/elective LC.
- After drainage, if the patient has higher surgical risk (µ), consider transfer to an advanced center.

Figure 3: Grade III (Severe) Acute Cholecystitis

Path 1: Start with antibiotics and general organ support.
Path 2: Assess for negative predictive factors: jaundice (total bilirubin ≥ 2 mg/dL), neurological dysfunction, or respiratory dysfunction.
Path 2a: If NO negative predictive factors are present AND the patient has favorable organ system failure (FOSF, meaning the cardiovascular or renal dysfunction is rapidly reversible), AND good performance status (PS, CCI ≤ 3 and ASA-PS ≤ 2), AND treatment is at an advanced center, then early LC can be considered.
Path 2b: If negative predictive factors are present OR the patient has poor PS OR treatment is not at an advanced center, then urgent/early GB drainage is required.
After drainage, if the patient has good PS, proceed with delayed/elective LC.
After drainage, if the patient has poor PS, continue observation and supportive care.

Important Reminders

In ALL grades, perform blood and bile cultures if the clinical picture warrants it (especially in Grade II and III).
Always consider the potential for surgical difficulty during LC. Be prepared to employ bail-out procedures to prevent bile duct injury.

Adapted from 'Tokyo Guidelines 2018: Diagnostic criteria and severity grading of acute cholecystitis,' Journal of Hepato-Biliary-Pancreatic Sciences, 2018. © The Authors. Published by Wiley Periodicals, Inc. on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/jhbp.516.

Introduction

Cholecystitis, the inflammation of the gallbladder, is a frequent encounter for surgical residents. This article provides a comprehensive review encompassing the pathophysiology, diagnosis, and management of cholecystitis, with a focus on practical aspects relevant to surgical residents.

I. Pathophysiology & Etiology: Back to the Basics

1. What happens in cholecystitis?

Obstruction: Cholecystitis typically starts with an obstruction of the cystic duct, most commonly due to gallstones. This obstruction leads to bile stasis and increased pressure within the gallbladder.
Inflammation: The trapped bile irritates the gallbladder wall, triggering an inflammatory response. This initially causes edema and wall thickening, which can progress to ischemia, necrosis, and eventually perforation.
Bacterial Infection: In many cases, bacteria from the gut (such as E. coli, Klebsiella, and Enterococcus) can enter the stagnant bile, causing a secondary bacterial infection that worsens the inflammation.

2. What causes cholecystitis?

Gallstones (Calculous Cholecystitis): The most common cause, accounting for 90-95% of cases. These stones, made of cholesterol or bile pigments, can obstruct the cystic duct.
Acalculous Cholecystitis: Occurs without gallstones, often in critically ill patients, those with significant trauma, or following major surgery. It is thought to be caused by decreased gallbladder motility, bile stasis, and ischemia.

II. Diagnosis: Connecting the Dots

A. Clinical Presentation:

History:
- RUQ pain: Typically colicky, severe, and may radiate to the right shoulder or back. Worsens after fatty meals.
- Nausea & Vomiting: Commonly associated symptoms.
- Fever: Indicates systemic inflammation and possible infection.
Physical Examination:
- RUQ Tenderness: Hallmark sign, localized to the gallbladder area.
- Murphy's Sign: Sharp pain and inspiratory arrest upon deep palpation of the RUQ during inspiration.
- RUQ Mass: May be palpable in cases of severe inflammation or empyema.

B. Laboratory Findings:

Elevated WBC count: Typically above 10,000/mm³, with a left shift (increased neutrophils) suggesting bacterial infection.
Elevated CRP: A non-specific marker of inflammation, often significantly elevated in cholecystitis.
Elevated Liver Enzymes (AST, ALT): Mild elevations may be seen due to inflammation near the liver.
Elevated Bilirubin: May indicate common bile duct obstruction (choledocholithiasis).

C. Imaging Studies:

1. Ultrasonography (US):
- First-line Imaging: Non-invasive, widely available, and highly accurate for diagnosing cholecystitis.
- Key Findings:
  - Gallstones: Echogenic structures with posterior acoustic shadowing.
  - Gallbladder Wall Thickening: > 4 mm (normal is < 3 mm).
  - Pericholecystic Fluid: Anechoic fluid collection surrounding the gallbladder.
  - Sonographic Murphy's Sign: Pain elicited by the transducer pressure over the gallbladder.
2. Computed Tomography (CT):
- Useful when US is inconclusive: Can better define complications like perforation, abscess, and pancreatitis.
- Key Findings:
  - Wall thickening and pericholecystic fluid: Similar to US.
  - Gallbladder distention: Enlarged gallbladder with air-fluid levels in emphysematous cholecystitis.
  - Pericholecystic inflammation: Fat stranding and fluid around the gallbladder.
3. Magnetic Resonance Imaging (MRI/MRCP):
- Provides excellent anatomical detail: Useful for evaluating bile duct anatomy, especially for suspected choledocholithiasis.
- Key Findings:
  - High signal intensity of gallbladder wall: On T2-weighted images, indicating edema and inflammation.
  - Biliary obstruction: Dilated bile ducts proximal to the obstruction.

III. Severity Grading: Guiding Treatment Decisions

The TG18 classifies cholecystitis into three grades to help tailor management strategies:

Grade I (Mild):

Criteria:
- No organ dysfunction.
- Mild local inflammation (e.g., tenderness, wall thickening on US).
Management:
- Conservative Treatment:
  - NPO: Rest the gallbladder by avoiding oral intake.
  - IV Fluids: Maintain hydration and electrolyte balance.
  - Analgesia: NSAIDs (e.g., ibuprofen 400-800mg every 6-8 hours, ketorolac 15-30mg IV every 6 hours) for mild to moderate pain; opioids (e.g., morphine 2-4mg IV every 4-6 hours, hydromorphone 0.2-0.4mg IV every 2-4 hours) for severe pain.
  - Antibiotics: Target common biliary pathogens (see section IV for details).
- Elective Laparoscopic Cholecystectomy: Ideally performed after the acute inflammation subsides.

Grade II (Moderate):

Criteria:
- One or more of the following:
- Elevated WBC count (> 18,000/mm³)
- Palpable tender mass in RUQ
- Symptoms for > 72 hours
- Marked local inflammation (e.g., gangrenous cholecystitis, pericholecystic abscess)
Management:
- Conservative Treatment: Similar to Grade I, but may require closer monitoring.
- Early Laparoscopic Cholecystectomy: Ideally within 72 hours of presentation, especially for cases with gangrenous or complicated cholecystitis.

Grade III (Severe):

Criteria: Organ dysfunction in any system (cardiovascular, neurological, respiratory, renal, hepatic, hematological).
Management:
- ICU Admission: Essential for organ support and close monitoring.
- Aggressive Conservative Treatment:
  - NPO, IV Fluids, Analgesia, Antibiotics: As described above.
  - Organ Support: Tailored to the specific organ dysfunction (e.g., vasopressors for hypotension, mechanical ventilation for respiratory failure).
- Percutaneous Cholecystostomy: Consider for critically ill patients who cannot tolerate surgery.
- Delayed/Interval Laparoscopic Cholecystectomy: Performed after stabilization of organ dysfunction and improvement of the inflammatory process.

IV. Management: A Resident's Approach

1. Antimicrobial Therapy:
- Empirical Therapy: Start broad-spectrum antibiotics that cover common biliary pathogens, considering local antibiograms and severity.
  - Mild/Moderate: Ceftriaxone 1-2g IV every 24 hours + Metronidazole 500mg IV every 8 hours. Alternatives: Piperacillin/Tazobactam 3.375g IV every 6 hours, Ampicillin/Sulbactam 3g IV every 6 hours.
  - Severe: Broader coverage with Piperacillin/Tazobactam 4.5g IV every 8 hours or Carbapenem (e.g., Imipenem/Cilastatin, Meropenem, Doripenem, Ertapenem) based on institutional protocols.
- Targeted Therapy: Adjust antibiotics based on culture results once available. De-escalation to narrower-spectrum antibiotics is encouraged.

Severity	Empirical Therapy	Alternatives
Mild/Moderate	- Ceftriaxone: 1-2 g IV every 24 hours + Metronidazole: 500 mg IV every 8 hours	- Piperacillin/Tazobactam: 3.375 g IV every 6 hours or - Ampicillin/Sulbactam: 3 g IV every 6 hours
Severe	- Piperacillin/Tazobactam: 4.5 g IV every 8 hours or - Carbapenem (e.g., Imipenem/Cilastatin, Meropenem, Doripenem, Ertapenem) based on institutional protocols

Targeted Therapy

Adjust antibiotics based on culture results once available.
De-escalation to narrower-spectrum antibiotics is encouraged.

2. Supportive Care:
- NPO & IV Fluids: Maintain adequate hydration and electrolyte balance.
- Pain Management: Aggressive pain control with NSAIDs or opioids as needed.
- Nausea & Vomiting Management: Antiemetics (e.g., ondansetron, promethazine) may be necessary.
3. Definitive Treatment: Cholecystectomy
- A. Laparoscopic Cholecystectomy (LC):
  - Gold Standard: Minimally invasive, offering faster recovery, less pain, and shorter hospital stays compared to open surgery.
  - Technique:
    - Pneumoperitoneum: Created using CO2 insufflation.
    - Trocar Placement: Typically four trocars are used for access and instrument manipulation.
    - Dissection: The gallbladder is carefully dissected from the liver bed, identifying and isolating the cystic duct and artery.
    - Critical View of Safety (CVS): Crucial step to avoid bile duct injury. Ensure you can clearly visualize:
    - The cystic plate (inferior wall of the liver bed).
    - Two structures entering the gallbladder (cystic duct and artery).
    - No other structures nearby (common bile duct, hepatic artery).
    - Clipping & Division: The cystic duct and artery are clipped and divided.
    - Gallbladder Removal: The gallbladder is extracted through one of the trocar sites.
  - Challenges in Acute Cholecystitis:
    - Inflammation & Fibrosis: Can obscure anatomical landmarks, making dissection challenging.
    - Increased Risk of Bile Duct Injury: Due to distorted anatomy and adhesions.
    - Difficult Dissection: May require advanced laparoscopic skills and meticulous technique.
B. Open Cholecystectomy:
- Reserved for Complicated Cases: When LC is not feasible or too risky due to:
  - Severe inflammation and adhesions.
  - Gallbladder perforation.
  - Bleeding complications.
  - Suspected malignancy.
- Technique: Involves a larger incision (typically right subcostal or midline) for direct visualization and dissection of the gallbladder.
C. Percutaneous Cholecystostomy (PC):
- Temporary Drainage Procedure: Performed under imaging guidance (US or fluoroscopy) to drain the gallbladder and relieve symptoms in critically ill patients.
- Technique:
  - Gallbladder Puncture: A needle is inserted into the gallbladder through the abdominal wall.
  - Catheter Placement: A drainage catheter is placed into the gallbladder and secured to the skin.
- Advantages: Minimally invasive and can be performed in patients who are not surgical candidates.
- Limitations: Temporary solution, does not address the underlying cause (gallstones), and carries a risk of bile leak or catheter dislodgment.
4. Postoperative Care:
- Pain Management: Continue pain control with oral or IV analgesics.
- Diet: Gradual reintroduction of a regular diet as tolerated.
- Ambulation: Encourage early ambulation to prevent complications like atelectasis and DVT.
- Wound Care: Monitor for signs of infection or bile leak.
- Follow-up: Ensure adequate follow-up to address any residual symptoms or complications.

Conclusion

Cholecystitis, the inflammation of the gallbladder, is a common condition encountered by surgical residents. Understanding its pathophysiology, diagnosis, and management is crucial for providing effective patient care. This article has provided a comprehensive review, emphasizing practical aspects relevant to surgical residents.

Key Points Recap:

Pathophysiology & Etiology:
- Obstruction: Usually caused by gallstones, leading to bile stasis and increased pressure within the gallbladder.
- Inflammation: Triggered by trapped bile, which can progress to ischemia, necrosis, and perforation.
- Bacterial Infection: Often secondary to the obstruction, commonly involving gut bacteria such as E. coli and Klebsiella.
Diagnosis:
- Clinical Presentation: RUQ pain, nausea, vomiting, and fever are key symptoms. Physical examination findings include RUQ tenderness, Murphy's sign, and sometimes a palpable mass.
- Laboratory Findings: Elevated WBC count, CRP, liver enzymes, and bilirubin.
- Imaging Studies: Ultrasound is the first-line imaging modality, with CT and MRI/MRCP as additional tools for more detailed assessment.
Severity Grading:
- Grade I (Mild): No organ dysfunction, mild local inflammation. Managed conservatively with NPO, IV fluids, analgesia, antibiotics, and elective laparoscopic cholecystectomy.
- Grade II (Moderate): Features more severe local inflammation. Managed with early laparoscopic cholecystectomy.
- Grade III (Severe): Associated with organ dysfunction. Requires ICU admission, aggressive conservative treatment, and percutaneous cholecystostomy for critically ill patients.
Management:
- Antimicrobial Therapy: Empirical broad-spectrum antibiotics, with adjustments based on culture results and de-escalation to narrower-spectrum antibiotics.
- Supportive Care: NPO, IV fluids, pain management, and antiemetics.
- Definitive Treatment:
  - Laparoscopic Cholecystectomy: The gold standard for most patients.
  - Open Cholecystectomy: Reserved for complicated cases.
  - Percutaneous Cholecystostomy: Temporary drainage for critically ill patients.
Postoperative Care:
- Pain management, gradual reintroduction of diet, early ambulation, wound care, and follow-up.