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Page 8 of 13 Matsuoka et al. J Cancer Metastasis Treat 2018;4:6 I http://dx.doi.org/10.20517/2394-4722.2017.85

died of recurrence, suggesting that evaluation of genetic changes using RT-PCR analysis can provide the
practical information for detecting free cancer cells in the peritoneal cavity with high sensitivity and for
selecting patients at high risk of peritoneal metastasis, leading to the prediction of chemotherapeutic efficacy
for these patients.

Extensive intra-operative peritoneal lavage (EIPL) therapy, i.e. extensively repeated dilution and complete
suction, serve as a very simple and non-aggressive prophylactic treatment for peritoneal metastasis of gastric
cancer patients with peritoneal free cancer cells . Yamamoto et al. described that the peritoneal relapse
[72]
[73]
rate of the patients with EIPL therapy was significantly lower than that of the patients without EIPL therapy.
Although intra-peritoneal free cancer cells were detected immediately after curative surgery using RT-PCR
[73]
analysis, no cancer cells were identified in the PLF after EIPL therapy . A recent study using ultra-rapid
quantitative RT-PCR has shown that the number of free cancer cells in PLF was serially diluted 3.8 × 10 ±
5
1.4 × 10 to 2.8 ± 1.5 cells/100 mL by 6 to 8 L of saline. Notably, CEA mRNA disappeared completely from
5
the PLF after seven to nine washes. Intraperitoneal chemotherapy followed by EIPL using an ultra-rapid
[74]
detection method may be acceptable for patients with free cancer cells in PLF after curative operation .
In a recent, the eligibility criteria for randomized controlled trials of neo-adjuvant chemotherapy or
hyperthermic intraperitoneal chemotherapy in locally advanced gastric cancer included the presence of
positive PLC at the staging laparoscopy . Recently previous study presented 103 patients with gastric cancer
[75]
who underwent staging laparoscopy and peritoneal metastasis was confirmed. Among them, 68 patients
received the intravenous and intraperitoneal paclitaxel plus oral S-1 as induction chemotherapy. PLF of
these patients was repetitively collected via intraperitoneal access ports. When a second laparoscopy showed
negative PLC, gastrectomy was considered. Significant prolonged survival of patients with CmRI values that
had once reduced to < 100 was identified by conversion gastrectomy. The OS of patients with a preoperative
CmRI value < 100 was significantly improved compared with that of those with a preoperative CmRI value
> 100 among patients who underwent conversion gastrectomy .
[37]
Based on these findings, we propose a treatment strategy for gastric cancer patients with positive PLC using
RT-PCR in Figure 1.

FUTURE PERSPECTIVES OF PLC BY GENETIC TECHNIQUES
Although numerous studies have presented that molecular analysis using RT-PCR may be useful for
the detection of free cancer cells, there are still several obstacles for realizing the clinical application of
genetically diagnosed PLC as a routine service. Namely, time-consuming, expensive, and relatively arduous
techniques compared with conventional cytology are pointed out, and the sensitivity is broadly variable
between laboratories; furthermore, procedures for quantitative assessment of free cancer cells are lacking.
Recently, experimental studies proposing rapid, accurate, more standardized, and cost-effective detection
methods have been reported. As described above, TRC can be a rapid and quantitative diagnostic technique
to target CEA mRNA because it does not require cDNA synthesis and the reactions of amplification,
and detection occur in a single tube, and take less than 1 h [36,76] . The reverse transcription-loop-mediated
isothermal amplification (RT-LAMP) technique is a promising candidate to reduce the time requirement.
In fact, there are several practical advantages to the RT-LAMP technique: it requires only simple reaction
procedures, the compact incubator or turbidimeter equipment costs less than $5000, and needs less than
1 h to obtain the final results . Among patients with negative cytology, those with a positive RT-LAMP
[10]
reaction had a shorter survival than those with negative RT-LAMP reaction results. The RT-LAMP method
may be an alternative method to determine the necessity or feasibility of surgery. Searching for a specific
diagnostic marker for peritoneal metastasis by a rapid PCR method may help patients avoid redundant
surgery and determine adequate preoperative chemotherapy.