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HIPEC (Hyperthermic Intraperitoneal Chemotherapy) is a surgical procedure used to treat peritoneal surface malignancies, combining cytoreductive surgery with direct intraperitoneal delivery of heated chemotherapy drugs.
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HIPEC hyperthermic intraperitoneal chemotherapy peritoneal carcinomatosis
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HIPEC (Hyperthermic Intraperitoneal Chemotherapy)
Definition
HIPEC is the intraoperative delivery of highly concentrated, heated chemotherapy (41-43°C) directly into the abdominal cavity, administered for 60-90 minutes immediately after cytoreductive surgery (CRS). It is the cornerstone treatment for peritoneal surface malignancies (PSMs).
Rationale / Mechanism of Action
The combination of heat and chemotherapy works through two distinct mechanisms:
- Direct antitumor effect of hyperthermia - heat alone kills cancer cells, particularly those with poor blood supply
- Enhanced chemotherapy penetration - heat increases drug permeability into tissues and enhances the cytotoxic effect of agents like cisplatin, mitomycin-C, and oxaliplatin
Additionally, intraperitoneal delivery creates a pharmacokinetic advantage: very high local drug concentrations at the tumor site while systemic absorption remains low, reducing systemic toxicity.
- Fischer's Mastery of Surgery, 8th ed., p. 1005
Pathophysiology of Peritoneal Carcinomatosis
Cancer spreads to the peritoneum through:
- Shedding of cells from the primary tumor
- Transport via peritoneal fluid
- Attachment to the mesothelial lining
- Invasion of the submesothelial tissue
Common primary origins: ovary, colorectum, appendix, stomach, and less commonly pancreas and small bowel. "Milky spots" in the omentum create a proangiogenic environment that facilitates seeding.
- Fischer's Mastery of Surgery, 8th ed., p. 1004
Indications
HIPEC is indicated in carefully selected patients with peritoneal surface malignancies from:
| Primary Tumor | Status |
|---|---|
| Pseudomyxoma peritonei (appendiceal origin) | Standard of care |
| Colorectal cancer with peritoneal metastasis | Curative intent (low-moderate PCI) |
| Ovarian cancer | After interval debulking surgery |
| Gastric cancer with peritoneal metastasis | Selected cases |
| Mesothelioma (peritoneal) | Established indication |
- Bailey and Love's Short Practice of Surgery, 28th ed., p. 1113; Fischer's Mastery of Surgery, 8th ed.
Patient Selection - Peritoneal Cancer Index (PCI)
The PCI is the key prognostic and selection tool. The abdomen is divided into 13 regions (sites 0-12). Each site is scored 0-3 based on tumor nodule size:
- Score 0 = no tumor
- Score 1 = tumor ≤0.5 cm
- Score 2 = tumor ≤5 cm
- Score 3 = tumor >5 cm or confluent disease
Maximum PCI = 39. Higher PCI correlates with worse prognosis.
- Colorectal cancer: CRS + HIPEC generally not offered if PCI >20
- Gastric cancer: PCI >6 associated with poor outcomes
The Completeness of Cytoreduction (CC) score is also critical:
- CC-0: No visible residual disease (curative)
- CC-1: Residual nodules <2.5 mm
- CC-2: Residual nodules 2.5 mm - 2.5 cm
- CC-3: Residual nodules >2.5 cm
CC-0/CC-1 are the goal; CC-2/CC-3 are generally contraindicated.
- Fischer's Mastery of Surgery, 8th ed., p. 1005-1006
Surgical Technique
Step 1: Cytoreductive Surgery (CRS)
Described by Paul Sugarbaker, CRS removes all visible peritoneal disease:
- Total/partial peritonectomy (diaphragmatic, parietal, pelvic)
- Omentectomy
- Multivisceral resections as needed (bowel, spleen, uterus, etc.)
- Fulguration or en-bloc resection of liver surface nodules
Must be performed by trained surgeons in specialized centers.
Step 2: HIPEC Delivery
Two techniques:
- Open (Coliseum) technique: Abdomen held open by retractors, surgeon manually distributes the drug - better distribution but staff exposure risk
- Closed technique: Abdomen closed after catheter insertion - less exposure but uneven distribution
A heating perfusion apparatus circulates the drug at 41-43°C for 60-90 minutes. At completion, the chemotherapy solution is drained and removed.
Common HIPEC Drugs by Indication
| Indication | Drug(s) |
|---|---|
| Ovarian cancer | Cisplatin |
| Colorectal cancer | Mitomycin-C or Oxaliplatin |
| Pseudomyxoma peritonei | Mitomycin-C ± Cisplatin |
| Gastric cancer | Cisplatin + Mitomycin-C |
| Mesothelioma | Cisplatin + Pemetrexed |
Less commonly: Paclitaxel, Gemcitabine, Melphalan, Doxorubicin.
- Fischer's Mastery of Surgery, 8th ed., p. 1013-1014
Contraindications
- High PCI beyond threshold for specific tumor type
- Extraperitoneal metastases (liver parenchymal, lung, brain)
- Inability to achieve CC-0/CC-1 cytoreduction
- Poor performance status (ECOG >2)
- Significant hepatic/renal dysfunction (drug clearance impaired)
- Severe malnutrition (not corrected preoperatively)
Complications
Morbidity: 30-60%; Mortality: 1-5% in specialized centers
| Type | Examples |
|---|---|
| Surgical | Anastomotic leak, bowel fistula, hemorrhage |
| Hematologic | Myelosuppression (especially with mitomycin-C, oxaliplatin) |
| Renal | Nephrotoxicity (cisplatin-related) |
| Hepatic | Transient hepatotoxicity |
| Infectious | Wound infection, intra-abdominal abscess |
| Ileus | Prolonged postoperative ileus common |
Outcomes / Evidence
- Colorectal cancer: The landmark Verwaal trial (NEJM, 2003) showed median OS of 22.3 months with CRS+HIPEC vs. 12.6 months with systemic chemotherapy alone
- Ovarian cancer: Van Driel et al. (NEJM, 2018) showed interval CRS + HIPEC improved recurrence-free survival by 3.5 months and OS by 11.8 months vs. CRS alone
- Pseudomyxoma peritonei: 10-year survival up to 70% with CRS+HIPEC
- Peritoneal mesothelioma: Median OS improved to 40+ months vs. 6-12 months with systemic therapy
A recent systematic review (2025) of international guidelines found strong consensus for CRS+HIPEC in colorectal, appendiceal, ovarian, and peritoneal mesothelioma, with ongoing trials strengthening evidence for gastric cancer.
HIPEC vs. PIPAC
| Feature | HIPEC | PIPAC |
|---|---|---|
| Timing | During CRS (curative) | Standalone laparoscopic (palliative/neoadjuvant) |
| Mechanism | Liquid perfusion, heat | Pressurized aerosol |
| Setting | Combined with CRS | Palliative or neoadjuvant |
| Repeat | Single application | Can be repeated |
- Fischer's Mastery of Surgery, 8th ed., p. 1005
Summary
HIPEC represents a multimodal, regionally aggressive strategy for peritoneal surface malignancies. Its success depends on complete cytoreduction (CC-0), appropriate patient selection (PCI scoring), tumor histology, and performance in high-volume specialized centers. It is the standard of care for pseudomyxoma peritonei and peritoneal mesothelioma, with growing evidence in colorectal and ovarian cancers.
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