ANNALS OF SURGERY

Vol. 219, No. 2, 109-111

© 1994 J. B. Lippincott Company

Pseudomyxoma Peritonei

A Cancer Whose Biology Is Characterized by

a Redistribution Phenomenon
Gough and associates are to be congratulated on their pseudomyxoma peritonei is apparent in this article. Un-
valuable contribution to the literature of cancer surgery. certainty exists worldwide in regard to the optimal surgi-
Their scholarly and critical approach to this disease pro- cal management, and no definite recommendations for
cess has given us new and valuable information about an a surgical approach can be extracted from this article.
unusual problem. These authors have emphasized some Also, precise indications for regional therapies were not
clinical features of this disease that must be appreciated given, and the beneficial results of treatment were sug-
if proper management is to occur. gestive rather than definitive. This article presents an
First, pseudomyxoma peritonei is a treatable disease honest but scrambled list of indications for treatment
process. Its unfamiliarity should not lead us to abandon and management options that represents our current
therapeutic options even though no prospective random- state of ignorance in dealing with pseudomyxoma peri-
ized trials are available. Regional therapies can be tonei.
effective. Repeated surgical procedures and regional in- Perhaps, the major issue confounding optimal man-
traperitoneal therapy can prolong the patient's survival. I agement concerns a failure to understand the natural his-
agree with these authors that systemic chemotherapeutic tory of pseudomyxoma peritonei. Can we clearly estab-
treatments are often debilitating and rarely associated lish the clinical entity of pseudomyxoma peritonei? Is
with prolonged survival with a good quality of life. Sys- there a fundamental principle of tumor biology that this
temic chemotherapy is rarely indicated for this disease disease manifests that distinguishes it? I think that there
process, which is confined to the abdominal cavity. It is. Pseudomyxoma peritonei, whether it be of appendi-
should only be considered for patients who have no other ceal, ovarian, or colorectal origin, is a disease process
options. characterized by a redistribution phenomenon. Redistri-
Early in this commentary, I feel compelled to com- bution means that large volumes of tumor will be found
ment that patient selection is of paramount importance at some predetermined anatomic sites within the perito-
in achieving beneficial results with peritoneal carcino- neal cavity but will be absent or in a greatly reduced vol-
matosis. It cannot be emphasized too strongly that an ume at other sites. Pseudomyxoma peritonei will have
aggressive surgical approach to extensive carcinomatosis large-volume cancer in the greater omentum ("omental
from adenocarcinoma has high morbidity and mortality cake"), at the undersurface of the right hemidiaphragm,
rates but affords little benefit in terms of long-term sur- in the pelvis, in the right retrohepatic space, in the left
vival. This is in great contrast to the treatment for pseu- abdominal gutter, and at the ligament of Treitz. The
domyxoma peritonei. peritoneal surfaces of the bowel are completely free of
I compliment these authors on their attempt to dispel tumor; these surfaces are relentlessly moved by peristal-
the myth that pseudomyxoma peritonei is a benign con- tic activity. They are never extensively involved unless
dition associated with long-term survival in a large pro- there have been multiple prior surgical procedures. For
portion of patients. This is an aggressive disease process this unique pattern of cancer dissemination to occur,
with no survival in patients followed long term without several biologic requirements and physiologic phenom-
definitive treatment. In my opinion, this low-grade can- ena must be operating. Pseudomyxoma cells do not have
cer requires management that uses a well-organized adherence molecules exposed on the cell surface. This
strategy as early as possible in the course of the disease. lack of "stickiness" means that the tumor cell will not
The lack of a coherent state-of-the-art therapy for actively attach to an abdominal or pelvic surface. The
109
110 Sugarbaker Ann. Surg. * February 1994

tumor will progress by the production of mucus, exfolia-

tion of tumor cells, and a redistribution of these cells
around the abdomen, according to two physiologic
mechanisms. First, the mucinous tumor cells will accu-
mulate at the sites of peritoneal fluid reabsorption. Large
pores present on the peritoneal surface of the omentum
and the undersurface of the diaphragm are open lym-
/1
phatic lacunae.' This is the anatomic site where perito-
neal fluid is absorbed. Ascitic fluid that is drawn to these
areas by intraperitoneal fluid dynamics leads to an accu- ureater omentum Left
mulation of cancer cells beneath the right hemidi- abdominal
aphragm and within the greater omentum. Second, these
cells will settle by gravity within the dependent portions
e1 RdI ~~~~~~~~~~~~~~~~~
r 1l~~ o o.f.:p:::::::..
::. a ci f Peu
of the abdomen (intra-abdominal "puddles"). This
means the tumor will accumulate in large volumes
within the pelvis, within the right retrohepatic space, in
the left abdominal gutter, and at the ligament of Treitz
(Fig. 1).
In summary, we define pseudomyxoma peritonei as a
clinical entity characterized by (1) the presence of mu-
cinous ascites from a grade I cystadenocarcinoma, (2) re-
distribution of the tumor within the abdominal cavity to oma peritonei. Grade Imucinous cancer arising from the appendix as a
villous adenoma bursts through the thin wall of the appendix. It spreads
predictable anatomic sites, and (3) an origin usually from widely throughout the peritoneal cavity but does not invade past the peni-
the appendix or ovary. toneal surface; it progresses exuberantly on the surface. With extensive
With the new concept of this disease, I think that a new mucus production, it continues to exfoliate tumor cells widely into the free
strategy for management has evolved. It does not include peritoneal cavity. These grade tumor cells rarely metastasize through the
the use of repeated operations required over many years lymph channels or by hematogenous routes. Similarly, their cell surfaces
in an attempt to prolong survival. I favor a dose-inten- do not have the adhesion molecules to stick randomly to peritoneal sur-
faces. Therefore, the clinical feature that most distinctly characterizes
sive approach that combines maximal surgery and max- pseudomyxoma peritonei is its tendency to "redistribute" around the peni-
imal regional intraperitoneal chemotherapy. The sur- toneal cavity. Portions of the peritoneum that are in motion, such as vis-
gery includes a series of well-defined peritonectomy pro- ceral peritoneum on the bowel surface, are only sparsely seeded by the
cedures that can strip all disease from the parietal intra-abdominal disease spread. The abdominal surfaces that absorb peni-
toneal fluid, such as the greater omentum and undersurface of dia-
peritoneal surfaces and resect all visceral peritoneal sur- phragms, are coated by large numbers of tumor cells as fluid is concen-
faces that are involved. This leaves the abdomen visibly trated during months and years. The other mechanism of tumor redistribu-
disease free.2 In the early postoperative period, before ad- tion is simply gravity. Free-floating intraperitoneal tumor cells will puddle in
hesions form and tumor cells become entrapped within large volumes within the pelvis, within the right subhepatic space, within
fibrinous accumulations, intra-abdominal irrigation and the left abdominal gutter, and at the ligament of Treitz.
chemotherapy are used to destroy the few remaining
cancer cells.3 Treatment failure, if it occurs, is usually ease in a sarcoma tend to be those histologic types that
associated with a nonuniform intraperitoneal chemo- recur. The surgical observation is that recurrent sarcoma
therapeutic distribution. is more invasive, more liable to metastasize distantly,
If surgery and chemotherapy are combined as a single and more difficult to resect curatively at each subsequent
dose-intensive event, reoperation is necessary in only reoperation. Pseudomyxoma is different. The change
10% of patients. If it is required, subsequent surgical pro- that occurs with pseudomyxoma peritonei is a result of
cedures are almost always associated with a reduction in cancer regrowth in scar tissue. The pseudomyxoma cells
the extent of intra-abdominal cancer. Without intraperi- become entrapped in fibrinous material, grow out in scar
toneal chemotherapy, each reoperation becomes more tissue, and with repeated operations, become intimately
difficult until eventually surgical treatment is impossible involved with the visceral peritoneum. This means that
or its use is associated with very high morbidity and mor- each reoperation is associated with a more difficult dis-
tality rates. section with higher postoperative morbidity and mortal-
Related to this, I disagree with these authors that the ity rates. For this reason, I advocate complete cytoreduc-
biology of pseudomyxoma peritonei changes over time tion with the use of the required peritonectomy proce-
with multiple reoperations. This is known to be true of dures followed by early postoperative intraperitoneal
intra-abdominal sarcoma. The areas of high-grade dis- chemotherapy in all patients. Early dose-intensive treat-
Vol. 219 - No. 2 Vol. 219.No. 2 ~~~~~~~~~~~~~~~PseudomyxomaPeritonei 111

100% follow "an unremitting but prolonged clinical course."4

60% - Using the cytoreductive approach, this disease can and
60% - .WHC
(n=83) should be cured in a majority of patients. The survival
S
70%- rates of patients with pseudomyxoma who were treated
R 60% - ..M SK (n=17-). at the Washington Hospital Center, Memorial Sloan-
V
60% - Kettering Cancer Center, and the Mayo Clinic are shown
40%-
in Figure 2.4 These groups of patients may not be com-
A
30% -
pletely the same, and further follow-up is indicated.
L
There is a suggestion that the cytoreductive approach to
20%-
Mayo (=6 pseudomyxoma peritonei may be the most effective.
lo% -
Paul H. Sugarbaker, M.D.
20 40 60 60 100 120 140 160 1S0200 220 2402600 20300 Washington, D.C.
MONTHS

Figure 2. Overall survival rates of patients with pseudomyxoma peritonei.

Survival curves modified from the experience with pseudomyxoma perito- References
nei from the Washington Hospital Center (WHO), Memorial Sloan-Kettering
Cancer Center (MSK), and the Mayo Clinic (Mayo). The WHC experience
1. Feldman GB, Knapp RI. Lymphatic drainage of the peritoneal cav-
involves a treatment using peritonectomy procedures as required and ity and significance in ovarian cancer. Am J Obstet Gynecol 1974;
early postoperative intraperitoneal chemotherapy. The MSK experience 119:991-994.
involves repeated surgical procedures and systemic chemotherapy. The 2. Sugarbaker PH. Peritoneal carcinomatosis form large bowel and ap-
Mayo experience involves repeated surgical procedures and intraperito- pendiceal cancer: a new approach to treatment. Postgrad Adv Colo-
neal radioisotopes or chemotherapy. rectal Surg 199 1; IlI-X:1-14.
3. Sugarbaker PH, Graves T, deBruijn EA, et al. Rationale for early
postoperative intraperitoneal chemotherapy (EPIC) in patients with
advanced gastrointestinal cancer. Cancer 1990; 65:1495-150 1.
ment of this malignancy, as in all cancers, will have the
4. Gough DB, Donohue JH, Schutt AJ, et al. Pseudomyxoma perito-
highest probability for cure with the lowest morbidity nei: long-term patient survival with an aggressive regional approach.
and mortality rates. Ann Surg 1994; 219:.
Studies of pseudomyxoma peritonei bring this disease 5. Sugarbaker PH, Zhu B, Baneg Sepe G, Smookler B. Peritoneal car-
process into a new focus. This is a nonmetastasizing can-
cinomatosis from appendiceal cancer: results in 69 patients treated
by cytoreductive surgery and intraperitoneal chemotherapy. Dis Co-
cer withdevastating outcome because of local progres-
a
lon Rect 1993; 36:323-329.
sion if therapy is not definitive early on. These patients 6. Smith JW, Kemeny N, Caldwell C, et al. Pseudomyxoma peritonei
should be treated for cure. This disease does not need to of appendiceal origin. Cancer 1992; 70:386-40 1.