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Page 2 of 13 Matsuoka et al. J Cancer Metastasis Treat 2018;4:6 I http://dx.doi.org/10.20517/2394-4722.2017.85

[3]
considered the main cause of peritoneal dissemination . Therefore, cytological examination of peritoneal
lavage fluid (PLF) obtained at the time of surgery has been considered a useful tool to detect free cancer cells.
The peritoneal lavage cytological examination (PLC) has been regarded as a feasible and indeed, the most
effective method to predict peritoneal recurrence and survival in patients with gastric cancer .The Japanese
[4-6]
Gastric Cancer Association suggests that the presence of free cancer cells in the peritoneal cavity should be
considered an independent prognostic factor in patients with gastric cancer . In addition, positive PLC is
[7]
defined as distant metastasis in the seventh edition of the American Joint Committee on Cancer Staging .
[8]
Therefore, patients with positive PLC most likely will not derive a benefit from surgical procedure, and
should be offered systemic chemotherapy or palliative therapy. Recent progress in systematic chemotherapy
has resulted in the improvement of prognosis and has allowed the introduction of conversion surgery for
select patients who respond effectively to the chemotherapy. However, there are still many issues to address,
as critical evidence regarding the timing of conversion, optimal chemotherapy regimen(s), and period of
chemotherapy does not exist at present.

Conventional cytology to detect cancer cells in PLF has been performed routinely . However, the fact
[4]
that peritoneal recurrence can be detected in approximately 10% of patients with negative PLF cytology
suggests that this cytological examination might not be sufficient for the detection of free cancer cells and
prediction of peritoneal spread . A more sensitive method for detecting free cancer cells in the peritoneal
[9]
cavity is urgently needed. The ability to predict micrometastasis development would significantly advance
the therapeutic approach to gastric cancer. Over the last few decades, many investigators have proposed the
use of molecular diagnostic methods, such as reverse transcription-polymerase chain reaction (RT-PCR)
targeting various clinical fields, including detection of free cancer cells [3,10,11] . Hence, in an effort to achieve
early detection, the analysis of a patient’s “genetic signature” using PLF after curative surgery has been
employed in recent years, especially in gastric cancer. In this review, we discuss the current evidence and
future perspectives of PLC for gastric cancer.

METHODS
PubMed was searched for English articles using the medical subject headings “gastric cancer”, “peritoneal
lavage”, and “peritoneal washing”. Relevant articles from clinical trials and case reports since 1989 were
included, as well as background articles relevant to the disease processes of interest.

BACKGROUND OF PLC
To detect free cancer cells and to predict peritoneal metastasis, conventional PLC performed on PLF
obtained during surgery has been broadly used [4,12] . PLC is currently examined via Papanicolaou staining
and assessed by a cytopathologist. Positive free cancer cells in PLC have been shown to be an important
and independent prognostic factor in patients with gastric cancer . Thus, PLC has been recommended
[12]
in the Japanese Classification of Gastric Carcinoma from 1998 onward . However, conventional PLC is
[13]
positive in only 59% of patients with macroscopical peritoneal disease . Additionally, the conventional
[14]
cytology in patients without any macroscopic peritoneal metastasis after curative surgery shows much lower
sensitivity (5%-15%) [15,16] . Meanwhile, levels of traditional tumor markers associated with gastric cancer in
PLF have been calculated to obtain greater sensitivity. Carcinoembryonic antigen (CEA) is a glycoprotein
found in colon cancer; it plays a role in cell adhesion . Although CEA is not sufficient with regard to
[17]
diagnostic sensitivity and specificity for early gastric cancer, guidelines suggest that serum CEA levels should
be measured to predict recurrent gastric cancer . It has been reported that CEA levels in PLF accurately predict
[18]
peritoneal recurrence after a curative resection of gastric cancer . The addition of immunohistochemical CEA
[19]
measurement to conventional cytology resulted in increased sensitivity (26%) . Combined analysis of CEA
[20]
with other principal gastric tumor markers, such as CA72-4 or CA125, has been shown to enhance the
accuracy for predicting peritoneal relapse [21,22] . Regardless, the CEA measurement in PLF still has an about