Title | Introduction | Histopathology | Computed Tomography | Clinical Assessment Criteria | Pharmacokinetics of IP Chemotherapy
Appendix Cancer Morphology | Cytoreductive Surgery | Perioperative Intraperitoneal Chemotherapy | Results of Treatment


Introduction


Appendix tumors are unusual, accounting for 0.4% of all of the gastrointestinal tract malignancies. Although rare, the spectrum of malignant disease is complex and has lead to confusion in accurate description of the natural history of these tumors. Consequently, many errors in diagnosis and treatment have occurred. Perhaps the most glaring error in management occurs in women who have ovarian tumors as a result of a perforated primary mucinous tumor of the appendix. Appendiceal tumors present with peritoneal seeding in a majority of patients. Dissemination to lymph nodes or to liver is extremely unusual. Advanced treatments of peritoneal carcinomatosis or peritoneal adenomucinosis have changed these survival rates from zero to approximately 80% for all patients.


Figure 1

Clinical pathway for the treatment of appendiceal tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.



 

Carcinoid

Cyst-
adenocarcinoma

Adenocarcinoma

Adenocarcinoid

Linitis Plastica*
(Signet Ring)

Incidence

66%

20%

10%

Rare

Rare

Location

Tip of appendix

Variable

Base of appendix

Diffuse along
appendix wall

Diffuse

Major symptom

Incidental finding

Appendicitis,
mucinous ascites

Appendicitis

Appendicitis or
right lower
quadrant mass

Appendicitis

Prognosis

< 1 cm 100% cure
> 2 cm 50% cure

Localized 90% cure
Peritoneal seeding-
poor prognosis

Follows Duke's stages
A - 80% cure
B - 50% cure
C - 20% cure

84% cure
at 5 years

Poor

Clinical syndromes

Carcinoid

Pseudomyxoma
peritonei

Peritoneal
carcinomatosis

   

Treayment

< 1 cm appendectomy only
> 2 cm right colectomy +
cytoreductive surgery

Appendectomy +
intraperitoneal
chemotherapy +
cytoreductive surgery

Right colectomy +
intraperitoneal
chemotherapy

Appendectomy
only unless
advanced

Radical surgery +
intraperitoneal chemotherapy +

           

* In separating cystadenocarcinoma, adenocarcinoma, and signet-ring cancer, it must be remembered that these represent a spectrum of these and are not distinct clinical entities. Benign mucocoele is not included as an appendiceal tumor but is rather a cystic process.

Table 1

Survey of appendiceal tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.



 

Colon

Appendix

Adenocarcinoma incidence

85%

10%

Carcinoid incidence

< 1%

70%

Mucinous adenocarcinoma

10-15%

20%

Signet-ring adenocarcinoma

1/1,000

10-Jan

Mucinous adenocarcinoid

Not reported

Rare

Differentiation carcinoma

20% Well
60% Moderate
20% Poor

60% Well
20% Moderate
20% Poor

Associated malignancy

Unusual

Common

Table 2

Comparison of colorectal and appendiceal malignant tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.



   

Type of distribution of adenocarcinoma

 

Proximally
random

Redistributed

Fibrin entrapment

Character

Solid

Glazed

Scar encased

Tumor grade

High

Low

Any

Extraabdominal metastases

Likely

No

Any

Tumor texture

Solid or mucinous

Mucinous and layered

Scar encased

Omental cake

No

Yes

No

Diaphragmatic accumulation

No

Yes

No

Bowel surface implantation

Yes

No

Yes

Biophysical mechanism
of distribution

Cell surface
adhesion

Gravity,
peritoneal fluid flow
motionless surfaces

Fibrin
entrapment at
wound site

Adhesion enzymes on
cell surface

Yes

No

Either

Treatable tumor volume

Low

Any

Low

Mechanism of implant
density

Proximity

Peritoneal fluid flow,
gravity

Proximity to surgical
margins of resection

Ascites

Unusual

Usual, mucinous

No

Surgical setting:
primary vs. reoperative

Both

Both

Reoperative

Transcoelomic progression

Some

Yes

No

Size of cancerous implant

Multiple
diameters of
plaques

Multiple
thickness
of layers

Uniform size, depending
depending on progression
since previous operation.

Tumor character

Plaquelike

Layered

Nodular

Location

Proximal and
random

Excludes mobile
surfaces

Traumatized
sites

Table 3



Figure 2

Survey of appendiceal tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.



Figure 3

Comparison of colorectal and appendiceal malignant tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.



Figure 4

Characteristics of three distribution patterns for intraabdominal tumor emboli. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.



Figure 5

Two patterns of natural spread with invasive and non-invasive malignancy. Left: A random and proximal distribution was observed with aggressive tumors. Implants are in close proximity to the perforation site and are randomly distributes on nearby surfaces. Right: Redistributed tumor was observed with non-invasive mucinous tumors. The large volume of implants were within the greater omentum, beneath hemidiaphragms, and within the pelvis. The difference in surface adhesion molecules with invasive and non-invasive malignancy are likely to be the major factor causing the marked differences in the distribution of peritoneal carcinomatosis. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.



Figure 6

Distinguishing clinical features of peritoneal seeding in sarcoma, pseudomyxoma peritonei and adenocarcinoma. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.



Figure 7

Two types of fibrin entrapment. Cancer cells may be traumatically dispersed at the time of a surgical procedure. These cancer cells then become involved in the healing process that inevitably results after a cancer resection. The first phase of the healing process is the flooding of the wound with fibrin. The fibrin entrapment causes two different morphologic types of peritoneal recurrence. Individual tumor emboli that are present on peritoneal surfaces in low density will result in nodular masses distributed throughout the peritoneal surfaces of the abdomen and pelvis. A higher density of tumor seeding will cause fusiform masses. This high density seeding usually occurs along narrow margins of resection, especially those margins that have been surgically traumatized as part of the cancer resection. Fusiform masses result from a layering of tumor within the operative site, especially along vital structures or unresectable anatomic barriers such as bone or major blood vessels. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.



Figure 8

Correlation of distribution pattern and implant morphology. The four distribution patterns of proximal-random, redistribution, generalized, and fibrin entrapment are correlated with a distinct morphology of implants that is observed with each pattern. Adenocarcinoma is an invasive process whose cancer cells contain adhesion molecules on the cancer cell surface. Also, little or no mucus is produced by the tumor that would facilitate widespread dissemination within the abdomen and pelvis. Pseudomyxoma peritonei, in contrast, has no adhesion molecules on its surface and shows no invasive capabilities on peritoneal surfaces or into lymphatics or vascular channels. The tumor cells are suspended in a large volume of slippery fluid. These two properties together account for the widespread dissemination of epithelial cells that arise from ruptured appendiceal adenoma. The mucinous adenocarcinoma presents a hybrid pattern of distribution that shows features of the pattern seen with adenocarcinoma combined with the pattern seen with pseudomyxoma peritonei. Sarcomatosis occurs if there is a perforation of the tumor into the peritoneal cavity. The sarcoma nodules do not migrate, but become wedged into crevices within the abdomen and pelvis where they progress. In most instances, surgical trauma results in sarcoma spillage, and the sarcoma implants are seen on the traumatized peritoneal surfaces. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.



Figure 9

The tissue of origin of a malignancy will control the pattern of progressive intracholehemic dissemination. Sarcoma implants occur in much lower numbers that do adenocarcinoma implants. Sarcoma implants disseminate on peritoneal surfaces if hemorrhagic necrosis and rupture of the primary tumor occurs. These sarcoma implants are limited in number and do not increase in an exponential fashion. Implants of adenocarcinoma reflect the tissue of origin, in that implants will exfoliate malignant cells from their surface early in the progressive growth of the peritoneal nodule. This exfoliation process may rapidly cause a confluence of adenocarcinoma on a peritoneal surface. This causes a "cobblestone" appearance of surfaces involved by adenocarcinoma implants. From Ronnett B, Sugarbaker PH:



Figure 10

Photomicrograph of adenomucinosis after four cycles of intraperitoneal chemotherapy. The tissue shown in this photomicrograph was taken from the surface of this tumor. The tumor shows complete disruption of its architecture, with no viable epithelial cells remaining. (H&E x35).




Title | Introduction | Histopathology | Computed Tomography | Clinical Assessment Criteria | Pharmacokinetics of IP Chemotherapy
Appendix Cancer Morphology | Cytoreductive Surgery | Perioperative Intraperitoneal Chemotherapy | Results of Treatment