What is Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?

Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a specialized treatment technique that delivers heated chemotherapy directly into the peritoneal cavity during surgery to target peritoneal surface malignancies, improving drug penetration and enhancing cancer cell death through the synergistic effects of heat and chemotherapy. 1

Definition and Mechanism

HIPEC is a procedure that:

• Delivers chemotherapy in a heated solution perfused throughout the peritoneal space
• Is typically performed immediately after cytoreductive surgery (CRS)
• Utilizes heat (41-43°C) to increase chemotherapy penetration at the peritoneal surface
• Enhances cancer cell sensitivity to chemotherapy by inhibiting DNA repair 1
• Targets microscopic residual disease after visible tumor has been surgically removed

Technical Aspects

HIPEC can be administered using different techniques:

• Open technique: Provides optimal distribution of heat and cytotoxic solution but has disadvantages of heat loss and drug leakage 2
• Closed technique: Prevents heat loss and drug spillage, increases drug penetration, but may not ensure homogeneous distribution 2
• Laparoscopic HIPEC: A hybrid approach that combines advantages of both open and closed techniques 2

The procedure typically involves:

• Perfusion of chemotherapy for 60-90 minutes (depending on agent and dose)
• Maintaining intraperitoneal temperature at 41-43°C
• Using 3-6 liters of isotonic crystalloid solution as the vehicle for chemotherapy 3
• Specialized equipment including a HIPEC pump connected to inflow and outflow catheters 3

Clinical Applications

HIPEC is primarily used in:

1. Ovarian Cancer:

   • Strongest evidence supports its use with cisplatin at interval cytoreductive surgery after neoadjuvant chemotherapy for stage III epithelial ovarian cancer 1, 4
   • The M06OVH-OVHIPEC trial demonstrated improved recurrence-free and overall survival in this setting 1
   • NCCN Guidelines include HIPEC as an option for patients with stage III disease treated with neoadjuvant chemotherapy who show response or stable disease 1

2. Gastric Cancer with Peritoneal Metastasis (GCPM):

   • Used in conjunction with cytoreductive surgery for patients with low-volume peritoneal metastasis 1
   • Most beneficial for patients with low peritoneal cancer index (PCI) scores and possibility for complete cytoreduction 1
   • May have prophylactic role in high-risk patients undergoing gastrectomy 1

3. Colorectal Cancer with Peritoneal Metastasis:

   • Evidence is less definitive compared to ovarian cancer 5
   • Recent studies have not shown clear benefit when added to perioperative chemotherapy 5

Safety and Complications

HIPEC carries significant risks that must be weighed against potential benefits:

• Procedure duration: 300-600 minutes (median)
• Hospital stay: 8-24 days (median) 1
• Intraoperative/postoperative mortality: 0-7% (more recent trials report no deaths) 1
• Major complications (9-40% of patients) include: 1
  • Fistulas and abscesses
  • Infections (wound, sepsis, pneumonia)
  • Surgical wound dehiscence
  • Bowel perforation and ileus
  • Hemorrhages and venous thromboembolism
  • Renal dysfunction and respiratory failure
  • Pleural effusions and pneumothorax

Patient Selection

Careful patient selection is critical for optimizing outcomes:

• Best candidates have high-volume intraperitoneal disease but limited extraperitoneal spread 1
• Patients with peritoneal carcinomatosis who are at risk for widespread residual microscopic disease even after complete macroscopic resection 1
• Patients with distant extra-abdominal metastases are typically excluded 1
• For gastric cancer, those with low-volume peritoneal metastasis and potential for complete cytoreduction benefit most 1

Perioperative Considerations

Important perioperative management includes:

• Multi-disciplinary team approach (gynecologic/surgical oncologists, anesthesia, nursing, perfusionists, pharmacists) 3
• Pre-medication protocols to reduce hypersensitivity reactions, renal toxicity, and post-operative nausea 3
• For cisplatin-based HIPEC: administration of furosemide and mannitol one hour prior to chemotherapy 3
• Close monitoring of temperature, electrolytes, and glycemic control during the procedure 3
• Proper training in toxic waste management, spill protocols, and personal protective equipment 3

HIPEC represents an important treatment option for selected patients with peritoneal surface malignancies, particularly in ovarian cancer where high-quality evidence supports its use in specific clinical scenarios. The decision to use HIPEC must carefully balance potential survival benefits against the significant risks of the procedure.