What is the optimal treatment approach for a patient diagnosed with Pseudomyxoma peritonei, a rare clinical syndrome characterized by a primary mucinous tumor of the appendix?

Pseudomyxoma Peritonei: Optimal Treatment Approach

The optimal treatment for pseudomyxoma peritonei is complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), which should be performed at a specialized high-volume center with expertise in peritoneal surface malignancies. 1, 2

Definitive Treatment Strategy

Complete Cytoreductive Surgery + HIPEC

• Complete macroscopic tumor excision (complete cytoreduction) combined with HIPEC is the gold standard treatment for PMP arising from appendiceal mucinous neoplasms 1, 2
• This approach achieves 5-year survival of 87% and 10-year survival of 74% when complete cytoreduction is accomplished 2
• The procedure typically requires approximately 10 hours of operating time for extensive disease 1, 3

Standard Surgical Components

The complete cytoreductive procedure generally includes 1:

• Bilateral parietal and diaphragmatic peritonectomies
• Right hemicolectomy (given appendiceal origin)
• Radical greater omentectomy with splenectomy
• Cholecystectomy and liver capsulectomy
• Pelvic peritonectomy with or without rectosigmoid resection
• Bilateral salpingo-oophorectomy with hysterectomy in females

HIPEC Protocol

• Mitomycin C is the most commonly used agent during the hyperthermic intraperitoneal chemotherapy phase 2
• The heated chemotherapy is administered intraoperatively following cytoreductive surgery 1, 3

When Complete Cytoreduction Is Not Achievable

• Maximum tumor debulking should still be performed even when complete tumor removal is not feasible 1, 2
• Patients undergoing major tumor debulking (incomplete cytoreduction) have 5-year survival of 34% and 10-year survival of 23%, which is significantly lower than complete cytoreduction but still provides meaningful survival benefit 2
• Approximately 34% of patients undergo major debulking rather than complete cytoreduction 2

Critical Prognostic Factors

Completeness of Cytoreduction

• Complete cytoreduction was achieved in 66% (289 of 441) of patients in a large series, with probable cure in more than two-thirds of these patients 2
• The difference in survival between complete cytoreduction and debulking is dramatic: 74% vs 23% at 10 years 2

Unique Features of Low-Grade PMP

• Very extensive disease with high Peritoneal Carcinomatosis Index (PCI) may still be amenable to complete excision and cure, unlike other peritoneal malignancies 1
• Disease progression is typically slow and may remain asymptomatic until advanced stages 1
• The "redistribution phenomenon" causes tumor accumulation at specific sites (greater and lesser omentum, undersurface of diaphragm particularly on the right) with relative sparing of the small bowel 1

Perioperative Outcomes

• Postoperative in-hospital mortality: 1.6% 2
• Grade 3/4 morbidity: 7% 2
• These procedures have high morbidity and mortality risks, reinforcing the need for specialized center management 3

Referral to Specialized Centers

Patients with PMP must be managed at centers with extensive expertise in peritoneal surface malignancies, as adherence to evidence-based protocols at high-volume centers is associated with improved survival outcomes 4, 3

The rarity of this condition (PMP is uncommon) combined with the complexity and risks of definitive treatment necessitates centralization of care 3

Pathologic Confirmation

• Ensure proper pathologic classification, as PMP should be distinguished from peritoneal carcinomatosis secondary to mucinous adenocarcinoma 3
• The appendix is the most common primary site, though ovarian and pancreatic origins occur 5, 6
• Molecular profiling may reveal mutations in ATM, GNAS, and KRAS proteins 6
• Immunohistochemistry typically shows gastrointestinal-specific staining (CK20, CDX2, CK7, SATB2) 6

Common Pitfalls to Avoid

• Do not treat PMP with systemic chemotherapy alone as the primary modality—this disease requires surgical cytoreduction 1, 2
• Do not attempt CRS/HIPEC at centers without specialized expertise in peritoneal surface malignancies 3
• Do not assume that extensive disease (high PCI) precludes curative treatment, as PMP differs from other peritoneal malignancies in this regard 1
• Ensure appendectomy is performed in all cases to confirm or rule out appendiceal origin 7