1. Cytoreductive surgery (CRS) followed by intraperitoneal chemotherapy, either intraoperatively (HIPEC) or postoperatively, is the standard treatment for peritoneal surface malignancies like carcinomatosis and mesothelioma. 2. The extent of disease is measured by the peritoneal cancer index (PCI) and the completeness of cytoreduction (CC score), which help determine prognosis and likelihood of benefit from CRS and HIPEC. 3. Multiple clinical studies have shown median survival benefits of 2-4 times longer compared to systemic chemotherapy alone for conditions treated with CRS and HIPEC.

1. By
Ihab Samy Fayek
Lecturer of Surgical Oncology
National Cancer Institute – Cairo University
2014

2. Peritoneal carcinomatosis.
Mesothelioma.
Sarcomatosis.

3. Two essential components:
First, cytoreductive surgery (CRS) to resect
visible implants within the abdomen and pelvis
(Peritonectomy along with visceral resections was
developed to surgically deal with cancer on
peritoneal surfaces).
Second, local-regional chemotherapy
(intraperitoneal chemotherapy or hyperthermic
intraperitoneal chemotherapy HIPEC).

4. Lack of Clinical Evidence for Alternative
Management Strategies.
Natural History Studies Document the
Importance of Local-Regional Progression.
Validated Quantitative Prognostic Indicators.

5. A near total lack of scientific data to support an
alternative treatment plan.
Level 1 data regarding the effectiveness of systemic
chemotherapy for peritoneal carcinomatosis has not
been published.
The response to systemic chemotherapy is not the
same for all anatomic sites of metastatic disease.
Over the past decade, multiple phase 2 and 3 studies
with CRS and POC report a median survival benefit
two to four times greater than survival using systemic
chemotherapy.

6. Recurrence of the primary cancer isolated to the
surfaces of the abdomen and pelvis is a reality.
Isolated peritoneal surface progression of
abdominal or pelvic malignancy is not unusual.
Cancer cells at low density result in peritoneal
carcinomatosis at a distance from the primary
cancer resection.
Cancer cells at higher density become trapped
within raw surfaces at the resection site.

7. The same group of quantitative prognostic
indicators operates for all patients with peritoneal
surface malignancy.
Prognostic indicators are used to refine the
selection of patients to those most likely to benefit
and to exclude those who are unlikely to benefit.
Histopathology assessments, the peritoneal cancer
index (PCI), the completeness of cytoreduction
score (CC), and radiologic imaging by computed
tomography (CT) play a central role in refining
patient selection.

8. Mucinous appendiceal neoplasms Patients with
adenomucinosis: maximal survival benefit, while those
with mucinous carcinoma show survivals similar to that
for peritoneal carcinomatosis of colorectal origin.
Peritoneal Mesothelioma Seven different histologic
patterns of peritoneal mesothelioma contribute to three
distinct histologic groups that have a very different
prognosis following CRS with POC.
Poor prognosis for sarcomatoid, deciduoid, or biphasic
type; intermediate prognosis for papillary and epithelial
type; and excellent prognosis for low-grade or
multicystic type.

9. The PCI is an assessment combining lesion
size (0 to 3) with tumor distribution
(abdominopelvic regions 0 to 12) to quantify
the extent of disease within the abdomen and
pelvis as a numerical score.
It is calculated at the time of surgical
exploration of the abdomen and pelvis.
The higher the PCI, the less likely CRS and
POC will result in long-term survival.

10. The new definition of complete cytoreduction is
no visible evidence of cancer or only minute
nodules reliably penetrated by POC, a
completeness of cytoreduction score of 0 (CC-
0) or CC-1, respectively.
With few exceptions an optimal CC-0 or CC-1
score is necessary for long-term benefit with
CRS and POC.

11. CT of the chest, abdomen, and pelvis is an essential
tool in the selection of patients for CRS with POC.
Systemic metastases and spread to pleural surfaces
can be identified.
The location and quantity of mucinous carcinoma within
the peritoneal cavity can be accurately determined,
small bowel compartmentalization versus diffuse
involvement of the small bowel.
If the small bowel and its mesentery are coated by
tumor or a large mass of cancer occupies the epigastric
region, the likelihood of achieving complete
cytoreduction is small.

12. As determined by physical properties, some
chemotherapy agents are especially appropriate
for hyperthermic use in the peritoneal cavity after a
cytoreductive surgery has been completed.
Other chemotherapy agents are more appropriate
for early postoperative intraperitoneal
chemotherapy.
As experience with POC has accumulated, the use
of multiple-agent chemotherapy has evolved and
promises to be increasingly effective.
Heat targeting is the goal of treatment.

13. The cytoreductive surgical procedure involves
visceral resections and peritonectomy procedures
in an attempt to leave the abdomen visibly free of
cancer.
After the CRS is complete, tubes and drains are
positioned to facilitate inflow and outflow of the
chemotherapy solution.
The chemotherapy solution circulates through
roller pumps and a heat exchanger to maintain
moderate hyperthermia (42°C/109°F) within the
abdomen and pelvis.

14. The skin edges are elevated on a self-retaining
retractor (open method) or the skin closed
(closed method) in order to create a reservoir
for the hyperthermic chemotherapy solution.
Following the HIPEC treatment, access to the
abdomen and pelvis is re-established to
perform the intestinal reconstruction.
Mechanical and chemical washing of the
complete parietal and visceral surfaces by the
warm chemotherapy solution will prevent a
reimplantation of cancer cells following CRS.

15. The complexity originates from the treatment as
well as from the management of the complications.
The peak of the learning curve in the study of is
reached after approximately 130 procedures.
Surgical skill is undoubtedly the main component
of this learning process, but experience in handling
complications contributed to a decreased morbidity
and mortality.

16. Intra-abdominal seeding of tumor cells early in
the natural history of the disease with
neoplastic cells throughout the peritoneal
cavity.
Simple mucinous adenoma: A tumor with more
than 90% mucus, flat epithelial cells, no atypia,
and no mitoses had a good prognosis despite
extensive intra-abdominal spreading  DPAM,
disseminated peritoneal adenomucinosis

17. Peritoneal carcinoma (PCA): a primary tumor
with much atypia, abundant mitoses, and less
than 50% mucus has a prognosis similar to
colorectal carcinomatosis, even with much less
intra-abdominal spreading.
Peritoneal mucinous carcinoma (PMCA):
Intermediate prognosis.

18. Stage IV colorectal cancer is a very morbid
disease, with a 5-year survival rate of 10% and
a median survival of 14.4 months.
The prognosis is significantly worse when
peritoneal carcinomatosis (PC) is present, with
a median survival of 6.7 months versus 18.1
months without PC (P <.01).

19. At the initial diagnosis of colon cancer, the
peritoneal surface is involved with tumor in
10% to 15% of patients.
Besides the liver, the peritoneal surfaces are
the most common sites of cancer recurrence
after “curative” colorectal cancer resections.
Cancer progression occurs in as many as 50%
of patients who had an R0 resection.

20. The key issue is to determine whether palliative
(systemic chemotherapy) or curative (complete
cytoreductive surgery [CCRS] with HIPEC)
treatment is indicated.
Contraindications
1. The presence of metastases at another site.
2. A poor general status.
3. Extensive PC is likely to be unresectable in its
entirety (PCI >20).

21. Five years after surgery, no patient was alive if
the size of the residual tumor nodules
exceeded 2 mm after surgery, whereas 30% of
the patients were alive if CCRS was possible
(P <.0001).
Median survival was 63 months in the CCRS
with HIPEC group versus 24 months in the
systemic chemotherapy group.

22. Peritoneal dissemination is the most frequent
pattern of metastasis and recurrence with
gastric cancers.
PC occurs in 5% to 20% of patients being
explored for potentially curative resection.
Regarding the efficiency of this combined
procedure (CRS and HIPEC) remains
controversial for carcinomatosis (incurable?).

23. A median follow-up of 20.4 months, the overall
median survival was only 9.2 months but the 5-
year survival rate was 13%, with some long-term
survivors.
The combination of cytoreductive surgery with
HIPEC was the only therapeutic strategy that
reported survivors at 5 years.
Recently, a 5-year survival of 23% and a median
survival of 15 months, was obtained in patients
treated with complete macroscopic resection
(PCI<12).

24. The median overall survival was 30.3 months.
The factors significant for increased survival were
sensitivity to platinum response (P = .048),
completeness of cytoreduction score of 1 or 0 (P =
.025), carboplatin alone or combination (P = .011),
and duration of hospital stays of 10 days or less (P
= .021).
A 75% 5-year survival in those 55 years or less,
with the best survival in those with no visible
disease at the end of CRS.