This document provides information about Pseudomyxoma Peritonei (PMP), including its historical background, epidemiology, pathology, clinical presentation, diagnosis, and treatment. It discusses the various theories about its origin and pathogenesis. Treatment involves aggressive cytoreductive surgery to remove all visible tumor deposits, followed by hyperthermic intraperitoneal chemotherapy (HIPEC) to treat any remaining microscopic disease. Combined modality treatment with complete cytoreduction and HIPEC can achieve long-term remission or cure. Recent studies show the importance of surgical experience, as morbidity and mortality decrease with increasing number of procedures performed.

1. Pseudomyxoma Peritonei
(PMP)
Presented by: Dr Happy Kagathara
16th
February, 2013
Dept. of GI surgery and Liver Transplant
Sir Ganga Ram Hospital

2. • Introduction
• Historical background
• Epidemiology
• Pathology
– Origin
– Pathogenesis
– Histology
• Clinical presentation
• Laboratory Tests and Immunohistochemical Markers

3. • Tumor Assessment
– USG
– CT scan
– Peritoneal Cancer Index (PCI)
• Treatment
– Traditional surgical management
– Combined modality management
– HIPEC
• Summary

4. Introduction
• Enigmatic condition
• First described - primary peritoneal disease looking like a
myxoma
• Not a real myxoma nor primary peritoneal disease
• Disseminated disease from a primary lesion of one of
intra-peritoneal organs
• Sound definition is not available and ongoing discussion
around PMP

5. • Theory 1 (theory of “secretion”)
– Consider any condition with gelatinous material (mucinous
ascites) in abdomen and pelvis
– Intra-peritoneal extravasations of mucus secretion of
whatever cause
Limber GK, King RE, Silverberg SG. Ann Surg 1973;178:587-93
• Theory 2 (theory of “collection”)
– Consider as a clinical syndrome
– Intra-peritoneal collection of gelatinous material and
mucinous tumor cells
– Abdominal distension

6. Historical Background
• First reported by a gynecologist, R. Werth, in 1884
– Unusual reaction of the peritoneum to a jelly-like substance
in relation to an ovarian neoplasm.
Werth R. Arch Gynaecol Obstet 1884;24:100-18.
• The discussion regarding the etiology emerged in the first
quarter of the 20th century
– Naeslund suggested
• Reaction of the peritoneal surface to mucoid
material leads to metaplastic changes.
Cheng KK. J Pathol Bacteriol 1949;61:217-25, 4 pl
• Simultaneous occurrence of an appendiceal mucocele
and cystadenoma of the ovary with PMP

7. • At the end of the century new treatment strategy emerged
– Combination of extensive surgery with intra-peritoneal
chemotherapy
Sugarbaker PH et al. Dis Colon Rectum 1993;36:323-9

8. Epidemiology
• Incidence – 1-2/million/year
• Predominance of women - 2 to 3 times
• Found in 2/10,000 laparotomies
• Approximately 10% epithelial appendiceal neoplasm
develop PMP
• Increased to 20% in mucinous appendiceal neoplasms

9. Pathology
• Origin
– Appendix, generally mucinous adenoma
– Colon, stomach, pancreas, ovary, and urachus
– The primary tumor consists
• mucinous cystadenoma
• cystadenocarcinoma with low malignant potential

10. – Debate about origin in concurrent mucinous tumor at
appendiceal and ovarian sites
• Immunoreactivity tests
– PMP – +ve for CK18 and CK20 both, -ve for CK7
– Ovarian neoplasms - +ve forCK7
• Ovarian PMP deposits are secondary to a primary
mucinous epithelial appendiceal tumor
– “Redistribution phenomenon”
• Gravity accumulates deposits in the pelvis
• Irregular surface of the ovaries and fimbriae act
as a stepping stone for PMP tumor cells

11. Redistribution phenomenon

12. • Pathogenesis
Appendiceal mucinous neoplasm
Mucus production by tumor cells into the appendiceal lumen
Obstruction of the appendiceal base by tumor or fecal material
Intraluminal mucus accumulation
Appendiceal mucocele
Rising intraluminal pressure
Small perforation of the appendiceal wall or blow-out of the
mucocele

13. Slow leak or sudden release of mucus
Free mucinous epithelial tumor cells into the peritoneal cavity
Tumor cells continue to proliferate
Mucinous ascites production
• Free mucus at different abdominal sites, containing no or few
epithelial tumor cells
• This stage is called PMP

14. • Histology
– Previously, terminology applied to both benign and
malignant mucinous appendiceal neoplasms
• Variable and poor prognosis
– Ronnett et al proposed three subtypes
• Different pathological characteristics and prognoses
• Base on broad spectrum of aggressiveness
Ronnett BM et al. Am J Surg Pathol 1995;19:1390 –1408

15. – Disseminated peritoneal adenomucinosis (DPAM)
• Low-grade lesion
• Abundant extracellular mucin
• Lack of cytological atypia or mitotic activity
• Usually from mucinous neoplasms of the appendix
• Good prognosis
– Peritoneal mucinous adenocarcinoma (PMCA)
• High-grade metastatic adenocarcinoma
• Abundant mucinous epithelium with architectural and
cytologic features of carcinoma
• Derived from the appendix and colon

16. – Intermediate type PMP (PMCA-I)
• Predominant features of DPAM
• Also focal areas of PMCA
• Prognosis between that of DPAM and PCMA

17. – Misdraji et al classifies into;
• Low-grade appendiceal mucinous neoplasm (LAMN)
– Papillary or flat mucinous tumors
– Low-grade cytologic atypia
– Analogous to low-grade dysplasia in other parts of
the gastrointestinal tract
• High-grade mucinous adenocarcinoma (MACA)
– Destructive invasion of the appendiceal wall
– High-grade cytologic atypia
– Complex epithelial proliferation
– Aggressive clinical course than LAMN
Misdraji J et al. Am J Surg Pathol 2003;27:1089 –1103

18. Clinical Presentation
Sugarbaker PH et al. Adv Surg 1996;30:233-80
Esquivel J, Sugarbaker PH. Br J Surg 2000;87:1414-8
• 30 to 50% pts - “Jelly belly” (Abdominal distension)
• Intestinal obstruction associated with compressing tumor
and ascites
• 50 to 80% pts - local symptoms, reflecting the location of
the primary or metastatic tumor
– Appendicitis-like symptoms

19. • 20 to 30% of female pts
– Detection of ovarian mass
– Evaluation for lower abdominal pain, a pelvic mass,
menstruation problems or infertility
• 1 to 20% pts - coincidently detected on USG or CT scan
for whatever reason, at laparotomy, or during hernia
repair when mucus is found in the hernia sac
• < 1% pts - presenting with a suspected bladder tumor or
right femoral neuropathy

20. • Interval between the discovery of the primary
(appendiceal) tumor and the clinical diagnosis of PMP
– Vary significantly
– Approximately 2 yrs
– Up to 20 yrs interval
Smeenk RM et al. Eur J Surg Oncol 2008; 34:196-201
Darnis E et al. J Gynecol Obstet Biol Reprod (Paris) 16:343-53, 1987

21. Laboratory Tests and
Immunohistochemical Markers
• CA-125
– Gynecological marker to exclude an ovarian neoplasm
– Not widely used as a tumor marker
– Elevated in benign or inflammatory diseases
– Sensitivity – 60%
• Cytokeratin (CK) 20, CEA, and CDX-2 - +ve in primary
tumors of colorectal or appendiceal origin
• CK7 +ve in primary tumors of ovarian origin

22. • IL-9 +ve in 96% pts
• CEA elevation - 56 to 75% of pts
• CA 19-9 elevation - 58% to 67% of pts

23. Tumor Assessment
• USG abdomen:
– Useful appendiceal mucocele or PMP
– Usually in combination with CT
– Advantages
• Low costs
• Accessibility
• Possibility of immediate FNA Biopsy
– Disappointing
– Inconclusive
• Sparse cellular density of both low and high
grade lesions

24. • CT scan with oral, rectal, and IV contrast
– Gold standard diagnostic
– Mucinous ascites
• higher density (5 to 20 HU) compared to normal ascites
– Low attenuation of soft tissue masses
– Rim like calcifications
– Septae

25. – In earliest stage
• Mucus around the appendix and appendiceal primary
neoplasm or mucocele
– Visceral and mesenteric sparing - favorable post-surgery
prognosis
– In end-stage disease
• Entanglement of the gastric antrum, lesser omentum,
left sub-phrenic region, spleen and rectosigmoid

26. • Impression of the liver surface – “scalloping of the
hepatic margin”
• Displacement/compression of the intestines by the
excessive amount of mucus
– Criterias of non-resectibility
• Segmental obstruction of small bowel
• Tumor nodule >5cm diameter on small bowel surface or
adjacent to small bowel messentery

27. Pseudomyxoma peritonei throughout the subdiaphragmatic regions

28. Peritoneal cavity with mucinous tumor in the pelvis

29. Small bowel (Red arrow) centralization by compressive effect in disseminated peritoneal
adenomucinosis (Green arrow)

30. • Sugarbaker Peritoneal Cancer Index
– Used in decision making process as abdomen is explored
– Size of intra-peritoneal nodules must be assessed
– Lesion Size score (LS) is used
• LS 0 – No visualization of malignant deposits in
particular abdomino-pelvic region
• LS 1 - Nodules <0.5cm
• LS 2 - Nodules 0.5 – 5 cm
• LS 3 - Nodules > 5 cm

31. • Maximum score – 39 (13X3)
– Number of nodules is not scored
– Only size of largest nodule is scored
– Regions – 13
• Abdomino-pelvic regions – 9
• Small bowel regions – 4

33. • Score <12 – Favorable prognosis
Berthet B et al. Eur j Cancer 1999; 35:413-9
– Pitfalls
• Non-invasive malignancy
– Large mass of non-invasive tumor can be
completely cytoreduced
– Pseudomyxoma peritonei, grade I sarcoma, minimal
invasive peritoneal mesothelioma
– E.g. PCI of 39 for these tumors can be converted to
0 by cytoreduction

34. • Invasive tumor at crucial anatomic sites
– E.g. Invasive tumor not resectable from CBD cause
poor prognosis even with low PCI
– Act as systemic disease in assessing prognosis with
invasive cancer.

35. • Completeness of Cytoreduction (CC) scoring system
– Scores
• CC 0 - En bloc resection of tumor mass with clear
margins
• CC 1 - Residual implants of < 2.5 mm
• CC 2 - Residual implants of 2.5 to 25 mm
• CC 3 – Residual as implants > 25 mm
– Predictibility
• Morbidity
• Disease-free survival
• Overall survival

36. Treatment
• Traditional Surgical Treatment
– Consists of
• Cytoreductive surgery
• Removal of all mucinous ascites
• ± Additional modalities
– Long-term survival could be achieved by surgery alone

37. – MSKCC- NY
• Aim – Symptom management
• 97 pts
• Mean of 2.2 de-bulking operations
• Complete cyto-reduction – 54%
• Survival was independently associated with;
– Low-grade pathologic subtype
– Ability to achieve complete cytoreduction
Miner TJ et al. Ann Surg 2005; 241:300-8

38. • Combined Modality Treatment
– Introduced in the 1990s by Sugarbaker
– Aims at achieving cure or at least long-term remission
– Aggressive cytoreductive surgery
• Parietal peritonectomy
– Greater omentectomy
– Splenectomy
– Stripping of the left diaphragm and the right
diaphragm

39. – Cholecystectomy
– Lesser omentectomy
– Antrectomy
– Pelvic peritonectomy
– Resection of recto-sigmoid and internal
gynecological organs
• Hyperthermic intraperitoneal chemotherapy (HIPEC)

40. – Mucinous tumor on parietal peritoneum
• Resection by high-power electrocautery with a ball-
tipped handpiece on high voltage pure cut
• Possible due to noninvasive behavior of PMP
• Dissected with finger and gauze if involving residual
visceral peritoneum on stomach, colon, or small bowel

41. – Concentration of disease in ileo-cecal region
• Ileo-cecum resection or a right hemicolectomy
• Ileum might be anastomosed or brought out as a
ileostomy
– Greater omentectomy
• Ligation of the gastric branches in the (right) gastric
arcade
• Contribute blood supply to stomach and left gastric
artery not be able to sustain adequate gastric blood
flow.
• Results in gastric paresis and postoperative ileus

42. • Therefore, gastrostomy and a high jejunostomy for
gastric emptying and nutrition.

43. • Hyperthermic intraperitoneal chemotherapy (HIPEC)
– Direct delivery into the peritoneal cavity
– Permits high concentrations of drugs directly toward the
tumor deposits
– Without important systemic side effects
– Hyperthermia enhance the penetration of cytostatic drugs
and synergism with various cytostatic drugs
– Effective only in minimal residual macroscopic disease
because of the limited penetration depth of drugs

44. – Should be performed intra-operatively before anastomoses,
to maximize uniform drug distribution and tumor exposure
Los G et al. Cancer Res 1992;52:1252-8
– In h/o prior surgery, adhesiolysis should be performed to
prevent nonuniform drug distribution
• All microscopic tumor residue is not eliminated
• Lead to recurrent disease
– Mitomycin as an intraperitoneal drug, either as single drug
or in combination
van Ruth S et al. Surg Oncol Clin N Am 2003;12:771-80.

45. – Also apply post-operative intra-peritoneal
chemotherapeutic treatment
– Continuing and further increasing exposure of tumor
residue
van Leeuwen BL et al. Ann Surg Oncol 2008; 15:745-53
– Two techniques
• Open
– Small bowel floats in drug solution

46. • Closed
– No loss of heat or drug
– Entire peritoneum is exposed
– Allow administration of drug under pressure
– Noninvasive, low grade disease eligible for complete
cytoreduction
– non-DPAM / high-grade disease excluded if involving 6 to
7 abdominal regions and/or small bowel

47. – Study by Smeenk and colleagues
• Report on learning curve
• 130 procedures, (133), Time period – 10 yrs
• The rate of complete (R1) cytoreduction increased from
15.4% to 49%
• Overall morbidity and mortality decreased from 68% to
28%
• In-hospital stay decreased from 24 to 17 days
Smeenk RM, Verwaal VJ, Zoetmulder FA. Br J Surg 2007;94:1408-14

48. – Yan and colleagues analyzed
• 140 consecutive (134) pts
• Compared the initial 70 pts with the subsequent 70 pts.
• Morbidity was reduced from 30% to 10%
• Delayed morbidity was reduced from 29% to 10%
• Independent risk factors for severe adverse events
– Small bowel resection
– Greater than 4 peritonectomy procedures
Yan TD et al. Ann Surg Oncol 2007;14:2270-80

49. – Chemotherapeutic agents
• Doxorubicin (15mg/m2
)
• Melphalan
• Mitomycin-C (12mg/m2
)
• Cisplatin (50mg/m2
)
• Gemcitabine
• Mitoxantrone
• Oxaliplatin
• Etoposide
• Irinotecan
• Paclitaxel
• Docetaxel
• 5-Fuorouracil (500 mg/m2
)
• Carboplatin

50. – Carriers of chemotherapeutic agents
• Isotonic salt solutions and dextrose solutions
– Rapid absorption
– Inability to maintain a prolonged high
intraperitoneal fluid volume
– Most commonly used
• Hypotonic solutions
– Cisplatin accumulates in tumor cells & enhances its
cytotoxicity
– High incidence of unexplained postoperative
peritoneal bleeding with oxaloplatin

51. • Hypertonic solutions
– High intra-peritoneal volume achieved for
prolonged duration
– Dilution of intra-peritoneal drug
• Isotonic high molecular weight solutions
– Prolonged high intra-peritoneal volume

52. – Duration for perfusion
• 410
C x 90 min
• 430
C x 30–40 min
• 420
C x 60 min
– Complications
• 30-45%
• Chemotherapy toxicity to kidneys, bone marrow, liver,
lungs- 2-5%

53. • Organ damage secondary to hyperthermia
• Surgical complications – 25-30%
– Small bowel fistula
• Moratlity - 0-5%

55. • Other treatment modality
– Laparoscopic approach
• allows thorough exploration of the abdomen
• irrigation and aspiration of the thick mucinous material,
and the instillation of mucolytic agents, 5% dextrose
solution.

56. Summary
• incidence is 2 per million per year with an unexplained female
dominance
• Redistribution phenomenon predicts location
• It is thought to be peritoneal disseminated disease from a primary
appendiceal mucinous epithelial neoplasm unless (very rarely)
proven otherwise with a normal appendix and a primary tumor
elsewhere
• It is suspected in case of intraperitoneal mucus with cellular content,
found during laparotomy or at physical examination (abdominal
girth)
• combination of (aggressive) surgical debulking with peritonectomy
and hyperthermic intraperitoneal chemotherapy seems to improve
the outcome.

57. • Patients with high-grade disease (peritoneal mucinous
carcinomatosis), disease extent with more than 5 involved
abdominal regions, and/or small bowel involvement should receive
palliative treatment because they do not benefit from aggressive
treatment approaches