Pseudomyxoma Peritonei

Pseudomyxoma peritonei is a clinical syndrome of progressive accumulation of mucinous ascites and mucinous implants in the peritoneal cavity, caused by dissemination of mucin-producing epithelial cells. The incidence is about 1 to 2 per million a year. The appendix is the source in about 90% (a low grade appendiceal mucinous neoplasm in most), and the remainder arise from the ovary, colon, pancreas, urachus or stomach.

Pathology grades: low grade (acellular or paucicellular mucin with bland epithelium, the commonest), high grade (cellular mucin with architectural complexity and marked atypia), and high grade with signet ring cells (the worst prognosis). KRAS mutations occur in about 80 to 90% and GNAS in about 50 to 70%.

Mechanism: tumor cells rupture through the appendix, and mucin follows the "redistribution phenomenon", accumulating in sites of low peristaltic movement (the pelvis, right subphrenic space, the greater omentum and the left paracolic gutter), and spares the small bowel surface. Fibrosis and mucin gradually obstruct the gut, and the disease does not usually invade parenchyma or spread through the lymph nodes.

Without treatment the disease progresses over years to death through bowel obstruction and malnutrition. With complete cytoreduction 10-year survival is about 60 to 70% in low grade disease and under 30% in high grade disease.

• Increasing abdominal girth, early satiety, weight loss and abdominal discomfort over months
• A new inguinal or umbilical hernia containing mucin
• Presentation as acute appendicitis, or a pelvic mass or ovarian mass in women
• Ascites that is gelatinous and does not shift
• Bowel obstruction in advanced disease
• Red flags: obstruction, fever (infected mucin), jaundice, severe malnutrition and rapidly increasing girth

1. CT of the chest, abdomen and pelvis with intravenous and oral contrast: low attenuation ascites that is septated, scalloping of the liver and spleen, omental cake, and calcified peritoneal implants. The small bowel is clumped centrally.
2. MRI for small bowel and mesenteric involvement.
3. Peritoneal cancer index by imaging or at operation (13 abdominopelvic regions, each scored 0 to 3 for lesion size, total 0 to 39) to predict the chance of complete cytoreduction.
4. Tumor markers: carcinoembryonic antigen, CA 19-9 and CA 125, raised in about 50 to 75%, and used for follow-up.
5. Biopsy (laparoscopic or image-guided) shows mucin with or without epithelial cells, with immunohistochemistry (CK20, CDX2, CK7).
6. Colonoscopy and gynecological assessment to identify other primary sources.

Differentials: malignant ascites, peritoneal carcinomatosis, tuberculous peritonitis, ovarian mucinous cystadenocarcinoma, cirrhosis, desmoplastic tumors.

1. Complete cytoreductive surgery with heated intraperitoneal chemotherapy is the standard treatment for resectable disease:
   • Peritonectomy procedures, omentectomy, splenectomy, cholecystectomy, resection of involved bowel segments, pelvic peritonectomy and hysterectomy with oophorectomy in women.
   • Aim for completeness of cytoreduction with no residual nodule over 2.5 mm.
   • Heated intraperitoneal chemotherapy at 41 to 42 degrees Celsius for 90 minutes: mitomycin C 30 to 35 mg/m2 as a single perfusion, or oxaliplatin 360 mg/m2 in 2 L/m2 5% dextrose for 30 minutes.
   • Anesthesia with epidural analgesia, goal-directed fluids, and intensive care postoperatively.
2. Prophylaxis: cefazolin 2 g IV with metronidazole 500 mg IV before incision, repeated if the procedure exceeds 4 hours, and enoxaparin 40 mg SC once daily for 28 days after surgery.
3. Perioperative nutrition: enteral feeding or parenteral nutrition at 25 to 30 kcal/kg a day with 1.5 g/kg of protein for malnourished patients.
4. Systemic chemotherapy: limited benefit in low grade disease. In high grade disease or signet ring features, use FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus then 2400 mg/m2 over 46 hours, every 14 days for 6 to 12 cycles) before or after surgery. Test for dihydropyrimidine dehydrogenase deficiency first.
5. Unresectable disease: repeated palliative debulking for obstruction and symptom control, with parenteral nutrition at home if required.
6. Complications: morbidity 30 to 40% (fistula, leak, sepsis, pancreatitis, bone marrow suppression, renal injury), mortality 1 to 3% in centres with experience, and recurrence in about 30 to 50%.

Follow-up with CT or MRI and tumor markers every 6 months for 2 years, then annually for 10 years. Counsel on prognosis, and on the need for repeat surgery.