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Mura et al. The peritoneal metastases from GC
the EpCAM antigen is expressed; on the contrary the treatment algorithm of advanced GC. [76]
peritoneal mesenchymal cells do not express it. The
[69]
rationale is strong, more evidence on results is needed. The identification of patients at risk of peritoneal
recurrence and the diagnosis of intra-peritoneal free
In a randomised study, a clinical effect was obtained cancer cells are probabilly two aspects of the same
after intraperitoneal infusion of catumaxomab problem. The majority of patients with positive cytology
in patients with symptomatic malignant ascites on peritoneal washing develop PC, although it also
secondary to EpCAM+ carcinomas, 66 out of 258 may occur in patients with negative cytological results.
notably from GC. Heiss and coll randomly assigned These observations indicate that conventional cytology
[69]
the patients to paracentesis alone, or to paracentesis lacks sensitivity for the detection of residual cancer cells
plus intraperitoneal catumaxomab. Puncture-free and the prediction of peritoneal spread. Many reports
survival was significantly longer in the group treated have emphasized the clinical significance of molecular
with catumaxomab compared to that in the control diagnosis using reverse transcriptase-polymerase
group (46 vs. 11 days, P < 0.0001) but median overall chain reaction analysis for more sensitive detection of
survival was similar between the two groups: 72 days GC cells in peritoneal washing. Fujiwara analyzed
[77]
in the catumaxomab group vs. 68 days in the control the survival of 123 patients with serosa-invading GC.
group (n.s). [69] The prognosis of the 29 patients with positive cytology
in the peritoneal washing was very poor, and most
Elias and his team from Gustave Roussy Institute of them died within 1 year after surgery. Among the
(Villejuif, France), with long-date experience in HIPEC 93 patients with negative cytology (CY0), 49 had a
for PC, recently proposed a randomized phase II positive genetic diagnosis and a significantly poorer
study, combining complete cytoreductive surgery with prognosis than those with negative genetic results.
intraperitoneal immunotherapy. The main inclusion More than half of the patients with positive PCR and
[70]
criteria of the protocol are PC of minimum or moderate CY0 developed peritoneal recurrence after surgery,
extension and macroscopic resection of all the lesions: while almost all patients with negative PCR and CY0
they just match the experience-based indications for had no peritoneal recurrence after surgery. These
[77]
HIPEC in PC from GC. As requested for HIPEC, results have been confirmed by many studies. All the
[54]
the complete resection of all macroscopic disease authors concluded that molecular diagnosis based
before starting the intra-peritoneal administration of on peritoneal washing is useful to predict peritoneal
catumaxomab is necessary. The immunotherapy could recurrence for patients with serosal invasion of GC;
therefore efficiently treat microscopic residual disease. PCR positivity has significant correlation with overall
survival and with peritoneal recurrence rate. [78-81] Up 2
DIAGNOSIS OF INTRA-PERITONEAL FREE patients of 3 with negative cytology can be positive to
CANCER CELLS AND IDENTIFICATION PCR detection; in other terms, when surgeons perform
OF PATIENTS AT RISK OF PERITONEAL R0 surgery (i.e. no macroscopic, microscopic and
RECURRENCE cytologic residual disease) for advanced GC, there is
high probability that it’s not true.
The methods of detecting peritoneal free cancer cells
represent an area in evolution. It’s well known that Molecular biological techniques are anyway time- and
the positive peritoneal cytology is according to the labour-intensive, and without yet diffuse application in
depth in invasion of the gastric wall, and that it has clinical practice. A new rapid gene detection system,
a prognostic value. [71,72] In the same way, it’s well One-step nucleic acid amplification has been recently
[82]
known that cumulative risk of peritoneal recurrence proposed. It shows potential for routine use in
is based on the infiltration of the gastric serosa. the clinical laboratory because of its simplicity and
[73]
Cytological examination of peritoneal washing at the rapidity. On the other hand, the molecular detection
time of primary tumor resection is frequently positive. of intraperitoneal GC cells is not only an independent
Free peritoneal cells are associated with an average prognostic factor, but also provides valuable clinical
survival of 4 months vs. 21 months for patients with information for choosing the appropriate treatment for
negative cytology. [71,74] cytology-negative patients: such patients are potential
candidate to intraperitoneal therapy, such as HIPEC,
According to the 7th edition of the American Joint immunotherapy or both.
Committee on Cancer positive cytology in the absence
of visible peritoneal implants is considered as M1 CONCLUSION
disease. Peritoneal washing for cytology (better
[75]
during a staging laparoscopy) is mandatory in staging/ The peritoneal metastatic spread of GC leads to PC, a
370 Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ September 18, 2016