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Mura et al. The peritoneal metastases from GC

of the “plasma-peritoneal barrier” which isolates
the peritoneal cavity from the effects of intravenous
chemotherapy. Although newer agents like S1 –
[36]
not available for Western Countries patients – and
docetaxel have been reported to have better results
against peritoneal metastases, yet the median survival
even with these drugs is only 18 months. [37,38]

Cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy
A poor response to systemic therapy provides the
rationale for a local-regional strategy for treatment.
The concept is that carcinomatosis is not to be
considered as systemic but compartment disease,
which can be attacked by cytoreductive surgery
(CRS) associated with loco-regional treatments such Figure 1: A phase of peritonectomy of diaphragmatic peritoneum;
as the hyperthermic intraperitoneal chemotherapy the arrows point to some nodules of carcinomatosis
(HIPEC). [5-7] During CRS are used well-codified
peritonectomy procedures with the removal of all
visible cancer with the affected peritoneum through
“peritoneal stripping”, always attempting to achieve
a complete cytoreduction [Figure 1]. The aim of
[39]
CRS is the complete macroscopic cytoreduction
as precondition for HIPEC. The residual disease is
classified intra-operatively using the completeness
of cytoreduction (CC) Score. The efficacy of intra-
peritoneal chemotherapy reaches its highest degree
in absence of visible residual disease (CC-0) or in
the presence of neoplastic residuals that are less or
equal to 2.5 mm (CC-1). [40,39] The main theoretical
advantage of intraperitoneal chemotherapy is that it
allows the direct application of high local concentration
of potentially effective drugs with minimal systemic Figure 2: HIPEC procedures for gastric carcinomatosis. Two
exposure and toxicity. [2,5,7] different models of surgical auto-retractors and two different HIPEC-
dedicated devices are shown. HIPEC: hyperthermic intraoperative
The neoplastic cells are more sensitive to the heat than intraperitoneal chemotherapy
the normal cells. Hyperthermia has a direct cytotoxic HIPEC are relatively safe. [44,45]
effect and an indirect effect by enhancing the action
of several anti-neoplastic drugs. Experimental studies Currently, CRS with HIPEC is increasingly being used
demonstrated that 42-43°C hyperthermia may have as a curative treatment of pseudomyxoma peritonei,
an important therapeutic effect on tumor tissue when peritoneal mesothelioma and selected patients with
applied alone; moreover hyperthermia synergically PC from colo-rectal or ovarian cancer. [46,5,7] The
enhances the chemosensitivity of neoplastic cells to CRS + HIPEC in PC arising from GC is a treatment
various antimitotic agents and allows deeper penetration still investigational. Several studies coming from
of drugs into tumor tissue. [41,42] During procedure of Europe and Far East show the possibility of long-
HIPEC, the chemotherapeutic agents are added into term survival with up to nearly 25% 5-year survival
the extra-corporeal circuit as soon as the abdominal rates in case of complete cytoreduction [Table 1].
temperature reaches 41.5-42.5°C [Figure 2]. [40] Glehen et al. [54] published in 2010 the results of a
retrospective French study of 1,290 patients with PC
Postoperative mortality after CRS and HIPEC is 2-4%, treated with HIPEC; 159 of them had PC of gastric
comparable to that following major gastrointestinal origin. In patients with a complete cytoreduction the
surgery. Morbidity is relatively high (25-41%) and 1-, 3-, and 5-year survival rates were 61%, 30%, and
seems to be related to the extension of CRS rather 23%, respectively. Completeness of cytoreduction
than to the HIPEC itself. [43,6,7] The anastomoses of total was the principal independent prognostic factor at
or subtotal gastrectomy in combination with CRS and multivariate analysis. [54,58] In a systematic review of
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ September 18, 2016 367