SciELO - Scientific Electronic Library Online

 
vol.71 issue12Serum Klotho (but not haplotypes) associate with the post-myocardial infarction status of older adults author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

  • text new page (beta)
  • English (pdf)
  • Article in xml format
  • How to cite this article
  • SciELO Analytics
  • Curriculum ScienTI
  • Automatic translation

Indicators

Related links

Share


Clinics

Print version ISSN 1807-5932On-line version ISSN 1980-5322

Clinics vol.71 no.12 São Paulo Dec. 2016

http://dx.doi.org/10.6061/clinics/2016(12)10 

REVIEW

Detection value of free cancer cells in peritoneal washing in gastric cancer: a systematic review and meta-analysis

Francisco Tustumi1  * 

Wanderley Marques Bernardo1 

Andre Roncon Dias1 

Marcus Fernando Kodama Pertille Ramos1 

Ivan Cecconello1 

Bruno Zilberstein1 

Ulysses Ribeiro-Júnior1 

1Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil


ABSTRACT

Intraperitoneal free cancer cells in gastric adenocarcinoma are associated with a poor outcome. However, the true prognostic value of intraperitoneal free cancer cells is still unclear, leading to a lack of consensus in the management of gastric cancer. The aim of the present study is to perform a systematic review and meta-analysis to analyze intraperitoneal free cancer cells-positive patients with regard to tumor oncologic stage, recurrence, grade of cellular differentiation, and survival rates and to analyze the clinical significance of intraperitoneal free cancer cells with regard to prognosis. Databases were searched up to January 2016 for prognostic factors associated with intraperitoneal free cancer cells, including oncologic stage, depth of neoplasm invasion, lymph nodal spread, differentiation grade of the tumor, and recurrence and survival rates. A total of 100 studies were identified. Meta-analysis revealed a clear association between intraperitoneal free cancer cells and a poor prognosis. intraperitoneal free cancer cells -positive patients had higher rates of nodal spread (risk difference: 0.29; p<0.01), serosal invasion (risk difference: 0.43; p<0.01), recurrence (after 60 months of follow-up, risk difference: 0.44; p<0.01), and mortality (after 60 months of follow-up, risk difference: 0.34; p<0.01). Intraperitoneal free cancer cells are associated with a poor outcome in gastric cancer. This surrogate biomarker should be used to guide therapy both prior to and after surgery.

Key words: Gastric Carcinoma; Peritoneal Washing; Peritoneal Lavage; Cytology; Carcinoembryonic Antigen; RT-PCR

INTRODUCTION

Peritoneal dissemination is the most common pattern of recurrence in gastric cancer, even after a potentially curative resection. This characteristic may be attributable to possible intraperitoneal dissemination of malignant cells already present at the time of surgery or to surgical manipulations. Current knowledge on intraperitoneal free cancer cell (IFCC) positivity in gastric cancer demonstrates that these cells are associated with a poor prognosis and advanced oncologic stages. Additionally, high recurrence rates, mainly due to peritoneal dissemination, and poor median survival are associated with cytology detection (1-3).

Based on these data, the Japanese Classification of Gastric Carcinoma: 3rd English Edition (4) and the 7th Edition of the AJCC Cancer Staging Manual: Stomach (5) consider conventional cytology positivity in peritoneal fluid to be an indicator of stage IV disease.

Several institutional protocols are used to manage IFCC-positive patients, including chemotherapy, prompt gastrectomy, neoadjuvant treatment, peritoneal infusion, hyperthermic peritoneal chemotherapy, or palliation alone. However, none of these techniques are accepted worldwide as a gold standard therapy.

The investigation of peritoneal washing for IFCCs in gastric cancer patients remains controversial. Little is known about the actual burden of IFCC positivity and its accuracy for predicting an outcome. Moreover, a lack of consensus exists in its routine practice, methods of detection (6), and association with clinical pathological variables.

Thus, the aim of this study was to perform a systematic review and meta-analysis, investigating patients positive for IFCCs detected via different methods, regarding the neoplasm oncologic stage, recurrence rates, grade of cellular differentiation, and survival rates and to analyze the clinical significance of IFCCs with regard to prognosis.

METHODS

The construction and modeling of the present study were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (7 8).

Database search

A literature search was performed in MEDLINE using the following search terms: (((“Stomach Neoplasms/cytology”[Mesh]) AND ((Peritoneum OR Peritoneal OR abdominal cavity OR ascitic fluid OR washing OR lavage)))) OR (((cytology AND gastric cancer)) AND ((Peritoneum OR Peritoneal OR abdominal cavity OR ascitic fluid))). Other databases searched included LILACS, CENTRAL, Cochrane, CINAHL, and Scopus as well as grey literature.

No attempts were made to locate unpublished material.

Inclusion criteria

  • Patients with confirmed gastric adenocarcinoma submitted to preoperative peritoneal washing/lavage evaluation (open, laparoscopic, or by paracentesis) for IFCCs (conventional cytology with Papanicolaou, Giemsa, or Hematoxylin-eosin staining); molecular methods, such as RT-PCR for carcinoembryonic antigen (CEA), cytokeratin (CK20), and melanoma-associated gene (MAGE); and immunohistochemistry.

  • Studies that evaluated the prognosis (i.e., oncologic stage, survival, recurrence rate, or grade of cellular differentiation).

  • Prospective or retrospective studies.

  • Studies selected by both of two reviewers.

Exclusion criteria

  • Data could not be extracted from pooled results.

  • Patients submitted to a neoadjuvant approach prior to the peritoneal washing/lavage procedure.

  • Presence of other primary malignancy.

  • Case series, case reports, animal models, conference proceedings, editorials, and letters.

  • Review articles and meta-analyses were excluded from meta-analysis.

  • Studies with no full-text.

Idiom

No restriction.

Search period

No restriction. The search was performed up to January 2016.

Outcomes

  • Recurrence rate

  • Recurrence site: lymph node, peritoneal, or other organs (local recurrence or hematogenous spread)

  • Mortality

  • Oncologic stage

  • Serosal invasion

  • Lymph node spread

  • Grade of cellular differentiation

Statistical analysis

Absolute numbers for the outcome parameters were extracted and analyzed with Review Manager Version 5.3 software (Copenhagen: The Nordic Cochrane Centre; The Cochrane Collaboration, 2014).

We performed subgroup analysis and sensitivity tests to explore the causes of statistical heterogeneity in which the effect of single studies on the heterogeneity value was tested. Forest plots were used for graphical exploration of heterogeneity. A funnel plot was used to identify publication bias.

RESULTS

 

Studies characteristics

Of the selected articles, 20 were excluded because they lacked the information necessary for meta-analysis, such as serosal invasion, oncologic stage, neoplasm dissemination, and grade of cellular differentiation. In total, 100 (1-3, 8-104) eligible trials were identified and reviewed, and 91 were included in the meta-analysis. Cumulatively, 16,913 gastric cancer patients were evaluated. In 41 studies analyzed, all patients were submitted to curative intention surgery.

We assessed the quality of the studies using the Newcastle-Ottawa Scale (NOS). In terms of study quality, the cohort studies were considered to be of fair (scores of 4–6) to good (scores of 7–9) quality, but two articles were considered low quality (scores of 1–3).

Of the 100 eligible trials, data describing conventional cytology were available for 68 papers; data regarding PCR-CEA were available for 27; and data regarding PCR-CK20 were available for 5. Other studies also evaluated Ber-Ep4, MAGE, RT-LAMP, or a combination of techniques used to detect IFCCs.

Most studies performed peritoneal washing/lavage similarly to the method described by Nakajima et al. (69). The peritoneal cavity was washed with 50 to 200 ml of normal saline. After stirring, the fluid was collected. Thirty-three studies collected fluid from the Douglas space, 16 collected fluids from the Douglas and left subphrenic spaces, and 5 collected fluid from the perigastric surroundings. The remaining studies collected fluid from different combinations of recesses. Peritoneal washing/lavage was performed by laparotomy in 81%, by laparoscopy in 15.2%, and by drainage tube in 3.8% of the studies.

Data were collected from 16 countries. The median follow-up across all studies was 36 months (range 12-108 months).

The prevalence of IFCCs ranged from 2 to 72%, with a median of 27%. Considering only conventional cytology studies, the median prevalence was 19.3% (range 2-61%). Considering only PCR-CEA, the median prevalence was 27.8% (range 15-63%). Considering only PCR-CK20, the median prevalence was 27.9% (range 15-39%).

IFCC and oncologic stage

The present study analyzed the oncologic stage according to the UICC/AJCC system 6th edition (105). For this purpose, IFCC detection alone was not considered stage IV.

The pooled data of the network meta-analysis showed that IFCC detection was associated with a significantly higher risk of stage III or IV compared with stage I or II (risk difference: 0.41; 95% CI: 0.33–0.49; n=4,258 patients; I2=88%, p<0.00001) (see Figure 1). The sensitivity analysis failed to identify outliers. A random-effects analysis method was used to adjust for inter-study heterogeneity.

Figure 1 Oncologic stage according to the AJCC 6th edition. A strong association was observed between IFCC detection and stages III and IV. 

For the subgroup analysis, conventional cytology studies (1-3,12,16-19,24,49,54,79,94,96) (risk difference: 0.34; 95% CI: 0.2–0.48; n=2,373 patients; I2=93%; p<0.00001) and PCR-CEA (31,36,38,49,77,93,94,97,104) (risk difference: 0.5; 95% CI: 0.36–0.63; n=1,073 patients; I2=83%; p<0.00001) were reviewed by comparing stage III or IV patients with stage I or II patients.

Comparable results were identified (risk difference: 0.32; 95% CI: 0.19–0.44; n=600 patients; I2=55%; p<0.00001) when analyzing studies that evaluated oncologic stages according to the UICC/AJCC system 7th edition (26 27,30 31 32 33,38,59,97).

IFCC and serosal invasion

The pooled data of the network meta-analysis showed that IFCC detection was associated with a significantly higher risk of serosal invasion than tumors that did not invade the serosa (risk difference: 0.43; 95% CI: 0.38–0.48; n=11,511 patients; I2=89%, p<0.00001) (see Figure 2). The sensitivity analysis failed to identify outliers. A random-effects analysis method was used to adjust for inter-study heterogeneity.

Figure 2 Evaluation of serosal invasion. An association between IFCC detection and serosal invasion was demonstrated. 

For the subgroup analysis, conventional cytology studies (2,3,10,11,15,16,18,19,22 23,25,29,34 35,40 39,41 42,43 44 45,46 47,48-57,60,62 63 65 66 67 68,69,70 71 73 74 75,78 80 82,81,83,86 87 88,90 91 92,94,96,98 99 100,101) (risk difference: 0.39; 95% CI: 0.35–0.43; n=2,374 patients; I2=93%; p<0.00001) and PCR-CEA (28,36-38,48-51,57,58,64,70,76,77,83,89,93,94,97,101,104) (risk difference: 0.51; 95% CI: 0.45–0.57; n=2,612 patients; I2=66%; p<0.00001) were reviewed.

IFCC and lymph node spread

The pooled data of the network meta-analysis showed that IFCC detection was associated with a significantly increased risk of lymph node spread compared to cancer with no lymph node involvement (risk difference: 0.29; 95% CI: 0.23–0.34; n=7,718 patients; I2=89%, p<0.00001) (see Figure 3). The sensitivity analysis failed to identify outliers. A random-effects analysis method was used to adjust for inter-study heterogeneity.

Figure 3 Evaluation of lymph node dissemination. A clear association between IFCC detection and lymph node metastasis was noted. 

For the subgroup analysis, conventional cytology studies (1-3,12,14,16,18,19,25,29,41,43,46,51,52,54-57,61,63,78,81,92,94,96 101) (risk difference: 0.25; 95% CI: 0.18–0.31; n=5,008 patients; I2=87%; p<0.00001) and PCR-CEA (31,36,38,48,57,58,64,76,77,93,94,97,104) (risk difference: 0.3; 95% CI: 0.15–0.45; n=1,464 patients; I2=93%; p<0.00001) were reviewed.

IFCC and grade of cellular differentiation

The pooled data of the network meta-analysis showed that IFCC detection was associated with a significantly increased probability of having poorly differentiated tumors compared to well or moderately differentiated tumors (risk difference: 0.15; 95% CI: 0.12–0.17; n=7,232; I2=65%, p<0.00001).

A sensitivity analysis was performed by repeating the network analysis after omitting 3 studies with a high risk of bias (31,102,103). The final result revealed a risk difference of 0.15 (95% CI: 0.13–0.18; n=6,784; I2=43%, p<0.00001) (see Figure 4).

Figure 4 Grade of cellular differentiation. A meta-analysis revealed the prognostic value of the grade of cellular differentiation. IFCC detection exhibited a stronger association with poorly differentiated tumors than with well or moderately differentiated tumors. 

For the subgroup analysis, conventional cytology studies (2,10,11,18,19,34,40,41,43,55-57,69,78,81,87,89,92,94-96,102,103) (risk difference after excluding 2 outliers (102,103): 0.17; 95% CI: 0.14–0.2; n=5,437 patients; I2=39%; p<0.00001) and PCR-CEA (31,57,64,77,93,94,97) (risk difference: 0.08; 95% CI: 0.01–0.15; n=805 patients; I2=55%; p<0.04) were reviewed.

IFCC and recurrence

The recurrence rate was assessed for gastric cancers treated with curative intention surgery.

The pooled data of the network meta-analysis showed that IFCC detection was associated with a significantly increased risk of recurrence. For recurrence after 24 months of follow-up (15,16,28,72), the risk difference was 0.38 (95% CI: 0.25–0.51; n=360 patients; I2=57%, p<0.00001). For recurrence after 60 months, the risk difference was 0.44 (95% CI: 0.32–0.56; n=2,176 patients; I2=88%, p<0.00001) (see Figure 5).

Figure 5 Recurrence rate. IFCCs were associated with a higher probability of recurrence after 60 months of follow-up. 

For IFCC-positive patients, the mean recurrence rate was 55.35% after 24 months and 68.73% after 60 months. For IFCC-negative patients, the mean recurrence rate was 16.77% after 24 months and 31.36% after 60 months.

IFCC and sites of recurrence

For gastric cancers treated with curative intent surgery, studies were assessed regarding peritoneal recurrence, lymph nodal recurrence, or recurrence in other organs.

For peritoneal recurrence, the presence of IFCCs predicted a risk difference of 0.48 (95% CI: 0.38–0.59; n=2,683 patients; I2=86%, p<0.00001) (see Figure 6). The sensitivity analysis failed to identify outliers. A random-effects analysis method was used to adjust for inter-study heterogeneity.

Figure 6 A strong association between IFCC detection and peritoneal recurrence was noted. 

For lymph nodal recurrence, the presence of IFCCs predicted a risk difference of 0.05 (95% CI: 0.00–0.1; n=1,553 patients; I2=29%, p=0.05) (see Figure 7).

Figure 7 IFCC detection can also predict a higher probability of lymph nodal recurrence. 

For local or hematogenous recurrence, the presence of IFCCs did not predict a poor prognosis (risk difference: 0.02; 95% CI: -0.03, 0.07; n=1,355 patients; I2=23%, p=0.22) (see Figure 8).

Figure 8 Hematogenous or local recurrence was not associated with IFCC detection. 

IFCC and mortality

The pooled data of the network meta-analysis showed that IFCC detection was associated with a significantly increased risk of mortality.

For mortality after 12 months of follow-up (9,13,15,20 21,56,57,63,85,92), the risk difference was 0.26 (95% CI: 0.19–0.33; n=1,765 patients; I2=48%, p<0.00001). One study was omitted after sensitivity analysis (92).

For mortality after 24 months (9,13,20,29,61,63,84,92), the risk difference was 0.4 (95% CI: 0.33–0.48; n=934 patients; I2=35%, p<0.00001). One study was omitted after sensitivity analysis (9).

For mortality after 60 months, the risk difference was 0.34 (95% CI: 0.29–0.38; n=1,811 patients; I2=50%, p<0.00001). Two studies were omitted after sensitivity analysis (69,72) (see Figure 9).

Figure 9 Mortality rate. IFCC detection was associated with a higher mortality rate after 60 months of follow-up. 

For IFCC-positive patients, the mean mortality rate was 43.5% after 12 months, 75% after 24 months, and 72.3% for studies that analyzed mortality after 60 months. For IFCC-negative patients, the mean mortality rate was 16.6% after 12 months, 43.2% after 24 months, and 41.2% after 60 months.

For the subgroup analysis, studies that exclusively evaluated patients who submitted to curative intention surgery were assessed.

For mortality after 12 months, the risk difference was 0.35 (95% CI: 0.24–0.45; n=799 patients; I2=13%, p<0.00001). One study was omitted after sensitivity analysis (92).

For mortality after 24 months, the risk difference was 0.34 (95% CI: 0.24–0.44; n=717 patients; I2=35%, p<0.00001). One study was omitted after sensitivity analysis (9).

For mortality after 60 months, the risk difference was 0.42 (95% CI: 0.37–0.47; n=995 patients; I2=58%, p<0.00001). One study was omitted after sensitivity analysis (18).

DISCUSSION

The present study evaluated the burden of IFCC positivity in gastric cancer by analyzing the individual data of each included study. The strengths of our study include the following: the study strategy was designed to be comprehensive; the inclusion and exclusion criteria and data extraction were determined to reduce bias; no idiom restrictions allowed the avoidance of cultural and racial bias; and this is the one of the first studies to analyze the true burden effect of IFCC positivity on recurrence rates (and sites of recurrence) and mortality rates. A limitation of this study was that some of the comparisons had a high level of heterogeneity.

Pecqueux et al. (106) also analyzed the relationship between IFCCs and survival and recurrence rates. However, they compared studies that evaluated recurrence and survival rates at different times, which compromised the validity of the findings.

Therefore, the present study assessed survival and recurrence rates at 1-, 2-, and 5-year follow-up evaluations. IFCC was associated with higher early and late mortality. Additionally, our study evaluated sites of recurrence and showed that recurrence was mainly due to peritoneal dissemination.

Similar to Pecqueux et al. (106), our study also revealed a high level of heterogeneity for recurrence rates. This finding could be explained by the different follow-up programs of each oncologic center, including different adjuvant therapies and methodologies for diagnosing recurrence.

To explore the causes of statistical heterogeneity, we performed subgroup and sensitivity analyses in which the effects of single studies on the heterogeneity value were tested. A funnel plot was used to identify publication bias. If publication bias was identified, the study was excluded from the analysis.

IFCC was associated with lymphatic spread (risk difference: 0.29; 95% CI: 0.23–0.34, p<0.00001) and lymph nodal recurrence (risk difference 0.05; 95% CI: 0.00–0.1, p<0.05). This result may be explained by confounding variables (IFCC actually could be associated with neoplasm depth, which would subsequently be associated with lymph nodal spread and recurrence). None of the trials explored these data, and future studies could investigate a possible link between lymphatic and peritoneal dissemination, which has been suggested by some authors (107).

IFCCs are also associated with locally advanced tumors, especially those with serosal invasion, but can also be found in earlier clinical stages of gastric cancer. Part of the mechanism by which advanced tumors disseminate into the peritoneum is likely associated with the area of serosal invasion (53,54,79), which could contribute to tumoral cell exfoliation and seeding into the peritoneal surface (108).

When assessing for subgroup analysis, different methods of detecting IFCC presented similar results for the prognosis. Both conventional cytology and PCR-CEA were associated with advanced stage cases, serosal invasion, nodal spread, and poorly differentiated neoplasms.

Most IFCC-positive patients who were treated with curative intent surgery likely experienced minimal to no benefit from the surgery, with most experiencing early recurrence (55.35% in 24 months). The survival rate of IFCC-positive patients was 25% after 2 years.

Accordingly, preoperative peritoneal washing/lavage in gastric cancer should be strongly advised for high surgical risk patients (e.g., the elderly, low status performance patients, and patients with incapacitating comorbidities). If IFCC positivity is determined, palliative therapy may be considered.

In low surgical risk and oncologic low risk (no serosa invasion, no lymph nodal spread, moderate or well differentiated neoplasm) patients, immediate surgery should be performed, and intraoperative peritoneal washing/lavage should be added. If IFCC positivity is determined, postoperative chemotherapy could be indicated. Clinical trials of hyperthermic intraperitoneal chemotherapy may be proposed.

The pooled data demonstrate that IFCC findings are an independent prognostic factor in gastric cancer. From this work, it can be concluded that the prognosis in surgically treated patients with gastric carcinoma is significantly affected by the presence of IFCCs at the time of gastrectomy and should guide gastric cancer management.

REFERENCES

1. Bentrem D, Wilton A, Mazumdar M, Brennan M, Coit D. The value of peritoneal cytology as a preoperative predictor in patients with gastric carcinoma undergoing a curative resection. Ann Surg Oncol. 2005;12(5):347-53, http://dx.doi.org/10.1245/ASO.2005.03.065. [ Links ]

2. Kodera Y, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, et al. Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection. J Surg Oncol. 1999;72(2):60-4, http://dx.doi.org/10.1002/(SICI)1096-9098(199910)72:2<60::AID-JSO3>3.0.CO;2-1. [ Links ]

3. Ribeiro U Jr, Safatle-Ribeiro AV, Zilberstein B, Mucerino D, Yagi OK, Bresciani CC, et al. Does the intraoperative peritoneal lavage cytology add prognostic information in patients with potentially curative gastric resection? J Gastrointest Surg. 2006;10(2):170-6, http://dx.doi.org/10.1016/j.gassur.2005.11.001. [ Links ]

4. Ajani JA, Bentrem DJ, Besh S, D’Amico TA, Das P, Denlinger C, et al. 2013 NCCN clinical practice guidelines in oncology: gastric cancer. 2013; Version 2. http://www.nccn.org. [ Links ]

5. Washington K. 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol. 2010;17(12):3077-9, http://dx.doi.org/10.1245/s10434-010-1362-z. [ Links ]

6. Brar SS, Mahar AL, Helyer LK, Swallow C, Law C, Paszat L, et al. Processes of care in the multidisciplinary treatment of gastric cancer: results of a RAND/UCLA expert panel. JAMA Surg. 2014;149(1):18-25, http://dx.doi.org/10.1001/jamasurg.2013.3959. [ Links ]

7. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1, http://dx.doi.org/10.1186/2046-4053-4-1. [ Links ]

8. Andrade RJ, Iturriza JF, Loyo EL, Martinez LE. Adenocarcinoma del Sistema digestivo: utilidad diagnóstica de la citología peritoneal. Rev Venez Oncol. 2005;17(2):79-88. [ Links ]

9. Asao T, Fukuda T, Yazawa S, Nagamachi Y. Carcinoembryonic antigen levels in peritoneal washings can predict peritoneal recurrence after curative resection of gastric cancer. Cancer. 1991;68(1):44-7, http://dx.doi.org/10.1002/1097-0142(19910701)68:1<44::AID-CNCR2820680109>3.0.CO;2-J. [ Links ]

10. Badgwell B, Cormier JN, Krishnan S, Yao J, Staerkel GA, Lupo PJ, et al. Does neoadjuvant treatment for gastric cancer patients with positive peritoneal cytology at staging laparoscopy improve survival? Ann Surg Oncol. 2008;15(10):2684-91, http://dx.doi.org/10.1245/s10434-008-0055-3. [ Links ]

11. Bando E, Yonemura Y, Takeshita Y, Taniguchi K, Yasui T, Yoshimitsu Y, et al. Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma. Am J Surg. 1999;178(3):256-62, http://dx.doi.org/10.1016/S0002-9610(99)00162-2. [ Links ]

12. Benevolo M, Mottolese M, Cosimelli M, Tedesco M, Giannarelli D, Vasselli S, et al. Diagnostic and prognostic value of peritoneal immunocytology in gastric cancer. J Clin Oncol. 1998;16(10):3406-11. [ Links ]

13. Bonenkamp JJ, Songun I, Hermans J, van de Velde CJ. Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancer. Br J Surg. 1996;83(5):672-4, http://dx.doi.org/10.1002/bjs.1800830526. [ Links ]

14. Brito AM, Sarmento BJ, Mota ED, Fraga AC Jr, Campoli PM, Milhomem LM, et al. Prognostic role of positive peritoneal cytology in patients with resectable gastric cancer. Rev Col Bras Cir. 2013;40(2):121-6, http://dx.doi.org/10.1590/S0100-69912013000200007. [ Links ]

15. Burke EC, Karpeh MS Jr, Conlon KC, Brennan MF. Peritoneal lavage cytology in gastric cancer: an independent predictor of outcome. Ann Surg Oncol. 1998;5(5):411-5, http://dx.doi.org/10.1007/BF02303859. [ Links ]

16. Chuwa EW, Khin LW, Chan WH, Ong HS, Wong WK. Prognostic significance of peritoneal lavage cytology in gastric cancer in Singapore. Gastric Cancer. 2005;8(4):228-37, http://dx.doi.org/10.1007/s10120-005-0343-6. [ Links ]

17. Dalal KM, Woo Y, Kelly K, Galanis C, Gonen M, Fong Y, et al. Detection of micrometastases in peritoneal washings of gastric cancer patients by the reverse transcriptase polymerase chain reaction. Gastric Cancer. 2008;11(4):206-13, http://dx.doi.org/10.1007/s10120-008-0483-6. [ Links ]

18. Euanorasetr C, Lertsithichai P. Prognostic significance of peritoneal washing cytology in Thai patients with gastric adenocarcinoma undergoing curative D2 gastrectomy. Gastric Cancer. 2007;10(1):18-23, http://dx.doi.org/10.1007/s10120-006-0402-7. [ Links ]

19. Fujimoto T, Zhang B, Minami S, Wang X, Takahashi Y, Mai M. Evaluation of intraoperative intraperitoneal cytology for advanced gastric carcinoma. Oncology. 2002;62(3):201-8, http://dx.doi.org/10.1159/000059566. [ Links ]

20. Fujimura T, Kinami S, Ninomiya I, Kitagawa H, Fushida S, Nishimura G, et al. Diagnostic laparoscopy, serum CA125, and peritoneal metastasis in gastric cancer. Endoscopy. 2002;34(7):569-74, http://dx.doi.org/10.1055/s-2002-33228. [ Links ]

21. Fujiwara Y, Okada K, Hanada H, Tamura S, Kimura Y, Fujita J, et al. The clinical importance of a transcription reverse-transcription concerted (TRC) diagnosis using peritoneal lavage fluids in gastric cancer with clinical serosal invasion: A prospective, multicenter study. Surgery. 2014;155(3):417-23, http://dx.doi.org/10.1016/j.surg.2013.10.004. [ Links ]

22. Fukagawa T, Katai H, Saka M, Morita S, Sasajima Y, Taniguchi H, et al. Significance of lavage cytology in advanced gastric cancer patients. World J Surg. 2010;34(3):563-8, http://dx.doi.org/10.1007/s00268-009-0355-1. [ Links ]

23. Fukuda N, Sugiyama Y, Wada J. Prognostic factors of T4 gastric cancer patients undergoing potentially curative resection. World J Gastroenterol. 2011;17(9):1180-4, http://dx.doi.org/10.3748/wjg.v17.i9.1180. [ Links ]

24. Fukumoto Y, Ikeguchi M, Matsumoto S, Inoue M, Osaki T, Fukuda K, et al. Detection of cancer cells and gene expression of cytokines in the peritoneal cavity in patients with gastric cancer. Gastric Cancer. 2006;9(4):271-6, http://dx.doi.org/10.1007/s10120-006-0390-7. [ Links ]

25. Funami Y, Tokumoto N, Miyauchi H, Ochiai T, Kuga K. Prognostic value of peritoneal lavage cytology and chemotherapy during surgery for advanced gastric cancer. Int Surg. 1999;84(3):220-4. [ Links ]

26. Han J, Lv P, Yu JL, Wu YC, Zhu X, Hong LL, et al. Circulating methylated MINT2 promoter DNA is a potential poor prognostic factor in gastric cancer. Dig Dis Sci. 2014;59(6):1160-8, http://dx.doi.org/10.1007/s10620-013-3007-0. [ Links ]

27. Hao YX, Zhong H, Yu PW, Qian F, Zhao YL, Shi Y, et al. Influence of laparoscopic gastrectomy on the detection rate of free gastric cancer cells in the peritoneal cavity. Ann Surg Oncol. 2010;17(1):65-72, http://dx.doi.org/10.1245/s10434-009-0703-2. [ Links ]

28. Hara M, Nakanishi H, Jun Q, Kanemitsu Y, Ito S, Mochizuki Y, et al. Comparative analysis of intraperitoneal minimal free cancer cells between colorectal and gastric cancer patients using quantitative RT-PCR: possible reason for rare peritoneal recurrence in colorectal cancer. Clin Exp Metastasis. 2007;24(3):179-89, http://dx.doi.org/10.1007/s10585-007-9067-9. [ Links ]

29. Hayes N, Wayman J, Wadehra V, Scott DJ, Raimes SA, Griffin SM. Peritoneal cytology in the surgical evaluation of gastric carcinoma. Br J Cancer. 1999;79(3-4):520-4, http://dx.doi.org/10.1038/sj.bjc.6690081. [ Links ]

30. Homma Y, Ushida S, Yamada M, Kobayashi H, Suzuki K. Positive peritoneal washing cytology in multiple cavities can predict poor prognosis of advanced gastric cancer patients. Ann Surg Oncol. 2010;17(2):455-60, http://dx.doi.org/10.1245/s10434-009-0764-2. [ Links ]

31. Horikawa M, Iinuma H, Inoue T, Ogawa E, Fukushima R. Clinical significance of intraperitoneal CD44 mRNA levels of magnetically separated CD45-negative EpCAM-positive cells for peritoneal recurrence and prognosis in stage II and III gastric cancer patients. Oncol Rep. 2011;25(5):1413-20. [ Links ]

32. Iida T, Iwahashi M, Katsuda M, Ishida K, Nakamori M, Nakamura M, et al. Prognostic significance of IL-17 mRNA expression in peritoneal lavage in gastric cancer patients who underwent curative resection. Oncol Rep. 2014;31(2):605-12. [ Links ]

33. Iitsuka Y, Kaneshima S, Tanida O, Takeuchi T, Koga S. Intraperitoneal free cancer cells and their viability in gastric cancer. Cancer. 1979;44(4):1476-80, http://dx.doi.org/10.1002/1097-0142(197910)44:4<1476::AID-CNCR2820440442>3.0.CO;2-R. [ Links ]

34. Iitsuka Y, Shiota S, Matsui T, Murata Y, Kimura A, Koga S. Relationship between the cytologic characteristics of intraperitoneal free cancer cells and the prognosis in patients with gastric cancer. Acta Cytol. 1990;34(3):437-42. [ Links ]

35. Ishigami S, Uenosono Y, Arigami T, Yanagita S, Okumura H, Uchikado Y, et al. Clinical utility of perioperative staging laparoscopy for advanced gastric cancer. World J Surg Oncol. 2014;12:350, http://dx.doi.org/10.1186/1477-7819-12-350. [ Links ]

36. Ishii T, Fujiwara Y, Ohnaka S, Hayashi T, Taniguchi H, Takiguchi S, et al. Rapid genetic diagnosis with the transcription-reverse transcription concerted reaction system for cancer micrometastasis. Ann Surg Oncol. 2004;11(8):778-85, http://dx.doi.org/10.1245/ASO.2004.12.043. [ Links ]

37. Ito S, Nakanishi H, Kodera Y, Mochizuki Y, Tatematsu M, Yamamura Y. Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients. Br J Cancer. 2005;93(9):986-92, http://dx.doi.org/10.1038/sj.bjc.6602802. [ Links ]

38. Jeon CH, Kim IH, Chae HD. Prognostic value of genetic detection using CEA and MAGE in peritoneal washes with gastric carcinoma after curative resection: result of a 3-year follow-up. Medicine (Baltimore). 2014;93(11):e83, http://dx.doi.org/10.1097/MD.0000000000000083. [ Links ]

39. Jeon CH, Shin IH, Park JB, Chae HD. Prognostic significance of MAGE in peritoneal washes in gastric carcinoma patients without peritoneal metastasis: results of a 5-year follow-up study. J Clin Gastroenterol. 2010;44(10):682-6, http://dx.doi.org/10.1097/MCG.0b013e3181d6bb0b. [ Links ]

40. Jiang CG, Xu Y, Wang ZN, Sun Z, Liu FN, Yu M, et al. Clinicopathological analysis and prognostic significance of peritoneal cytology in Chinese patients with advanced gastric cancer. ANZ J Surg. 2011;81(9):608-13, http://dx.doi.org/10.1111/j.1445-2197.2010.05536.x. [ Links ]

41. Jonas S, Weinrich M, Tullius SG, Al-Abadi H, Steinbrich R, Radke C, et al. Microscopic tumor cell dissemination in gastric cancer. Surg Today. 2004;34(2):101-6, http://dx.doi.org/10.1007/s00595-003-2666-4. [ Links ]

42. Kanetaka K, Ito S, Susumu S, Yoneda A, Fujita F, Takatsuki M, et al. Clinical significance of carcinoembryonic antigen in peritoneal lavage from patients with gastric cancer. Surgery. 2013;154(3):563-72, http://dx.doi.org/10.1016/j.surg.2013.03.005. [ Links ]

43. Kang KK, Hur H, Byun CS, Kim YB, Han SU, Cho YK. Conventional cytology is not beneficial for predicting peritoneal recurrence after curative surgery for gastric cancer: results of a prospective clinical study. J Gastric Cancer. 2014;14(1):23-31, http://dx.doi.org/10.5230/jgc.2014.14.1.23. [ Links ]

44. Kano Y, Kosugi S, Ishikawa T, Otani T, Muneoka Y, Sato Y, et al. Prognostic significance of peritoneal lavage cytology at three cavities in patients with gastric cancer. Surgery. 2015;158(6):1581-9, http://dx.doi.org/10.1016/j.surg.2015.04.004. [ Links ]

45. Katsuragi K, Yashiro M, Sawada T, Osaka H, Ohira M, Hirakawa K. Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection. Br J Cancer. 2007;97(4):550-6, http://dx.doi.org/10.1038/sj.bjc.6603909. [ Links ]

46. Ki YJ, Ji SH, Min JS, Jin SH, Park S, Yu HJ, et al. Test execution variation in peritoneal lavage cytology could be related to poor diagnostic accuracy and stage migration in patients with gastric cancer. J Gastric Cancer. 2013;13(4):214-25, http://dx.doi.org/10.5230/jgc.2013.13.4.214. [ Links ]

47. Kodera Y, Nakanishi H, Ito S, Mochizuki Y, Ohashi N, Yamamura Y, et al. Prognostic significance of intraperitoneal cancer cells in gastric carcinoma: analysis of real time reverse transcriptase-polymerase chain reaction after 5 years of followup. J Am Coll Surg. 2006;202(2):231-6, http://dx.doi.org/10.1016/j.jamcollsurg.2005.09.008. [ Links ]

48. Kodera Y, Nakanishi H, Ito S, Yamamura Y, Kanemitsu Y, Shimizu Y, et al. Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time reverse transcriptase-polymerase chain reaction: a sensitive predictor of outcome for patients with gastric carcinoma. Ann Surg. 2002;235(4):499-506, http://dx.doi.org/10.1097/00000658-200204000-00007. [ Links ]

49. Kodera Y, Nakanishi H, Yamamura Y, Shimizu Y, Torii A, Hirai T, et al. Prognostic value and clinical implications of disseminated cancer cells in the peritoneal cavity detected by reverse transcriptase-polymerase chain reaction and cytology. Int J Cancer. 1998;79(4):429-33, http://dx.doi.org/10.1002/(SICI)1097-0215(19980821)79:4<429::AID-IJC20>3.0.CO;2-Z. [ Links ]

50. Kodera Y, Nakanishi H, Ito S, Yamamura Y, Fujiwara M, Koike M, et al. Prognostic significance of intraperitoneal cancer cells in gastric carcinoma: detection of cytokeratin 20 mRNA in peritoneal washes, in addition to detection of carcinoembryonic antigen. Gastric Cancer. 2005;8(3):142-8, http://dx.doi.org/10.1007/s10120-005-0318-7. [ Links ]

51. Kodera Y, Nakanishi H, Ito S, Yamamura Y, Kanemitsu Y, Shimizu Y, et al. Quantitative detection of disseminated cancer cells in the greater omentum of gastric carcinoma patients with real-time RT-PCR: a comparison with peritoneal lavage cytology. Gastric Cancer. 2002;5(2):69-76, http://dx.doi.org/10.1007/s101200200012. [ Links ]

52. Kodera Y, Yamamura Y, Ito S, Kanemitsu Y, Shimizu Y, Hirai T, et al. Is Borrmann type IV gastric carcinoma a surgical disease? An old problem revisited with reference to the result of peritoneal washing cytology. J Surg Oncol. 2001;78(3):175-81, http://dx.doi.org/10.1002/jso.1144. [ Links ]

53. Koga S, Kaibara N, Iitsuka Y, Kudo H, Kimura A, Hiraoka H. Prognostic significance of intraperitoneal free cancer cells in gastric cancer patients. J Cancer Res Clin Oncol. 1984;108(2):236-8, http://dx.doi.org/10.1007/BF00402474. [ Links ]

54. Kostić Z, Cuk V, Bokun R, Ignjatović D, Usaj-Knezević S, Ignjatović M. Detection of free cancer cells in peritoneal cavity in patients surgically treated for gastric adenocarcinoma. Vojnosanit Pregl. 2006;63(4):349-56, http://dx.doi.org/10.2298/VSP0604349K. [ Links ]

55. La Torre M, Ferri M, Giovagnoli MR, Sforza N, Cosenza G, Giarnieri E, et al. Peritoneal wash cytology in gastric carcinoma. Prognostic significance and therapeutic consequences. Eur J Surg Oncol. 2010;36(10):982-6, http://dx.doi.org/10.1016/j.ejso.2010.06.007. [ Links ]

56. Lee SD, Ryu KW, Eom BW, Lee JH, Kook MC, Kim YW. Prognostic significance of peritoneal washing cytology in patients with gastric cancer. Br J Surg. 2012;99(3):397-403, http://dx.doi.org/10.1002/bjs.7812. [ Links ]

57. Li JK, Zheng M, Miao CW, Zhang JH, Ding GH, Wu WS. Peritoneal lavage cytology and carcinoembryonic antigen determination in predicting peritoneal metastasis and prognosis of gastric cancer. World J Gastroenterol. 2005;11(46):7374-7, http://dx.doi.org/10.3748/wjg.v11.i46.7374. [ Links ]

58. Li Z, Zhang D, Zhang H, Miao Z, Tang Y, Sun G, et al. Prediction of peritoneal recurrence by the mRNA level of CEA and MMP-7 in peritoneal lavage of gastric cancer patients. Tumour Biol. 2014;35(4):3463-70, http://dx.doi.org/10.1007/s13277-013-1458-8. [ Links ]

59. Lisiecki R, Spychała A, Pater K, Murawa D. Analysis of risk factors of positive peritoneal cytology in patients treated for gastric cancer - preliminary report. Pol Przegl Chir. 2015;87(10):506-12. [ Links ]

60. Majima T, Ichikura T, Mochizuki H. Prognostic significance of the cytologic features of free cancer cells in the peritoneal cavity of patients with gastric cancer. Surg Today. 2002;32(1):35-9, http://dx.doi.org/10.1007/s595-002-8110-6. [ Links ]

61. Makino T, Fujiwara Y, Takiguchi S, Miyata H, Yamasaki M, Nakajima K, et al. The utility of pre-operative peritoneal lavage examination in serosa-invading gastric cancer patients. Surgery. 2010;148(1):96-102, http://dx.doi.org/10.1016/j.surg.2009.11.025. [ Links ]

62. Mandorwski S, Lourenco LG, Forones NM. CA72-4 e CEA no soro e no lavado peritonial de doentes com câncer gástrico. Arq. Gastroenterol. 2002;39(1):17-21, http://dx.doi.org/10.1590/S0004-28032002000100004. [ Links ]

63. de Manzoni G, Verlato G, Di Leo A, Tomezzoli A, Pedrazzani C, Pasini F, et al. Peritoneal cytology does not increase the prognostic information provided by TNM in gastric cancer. World J Surg. 2006;30(4):579-84, http://dx.doi.org/10.1007/s00268-005-7901-2. [ Links ]

64. Marutsuka T, Shimada S, Shiomori K, Hayashi N, Yagi Y, Yamane T, et al. Mechanisms of peritoneal metastasis after operation for non-Serosa-invasive gastric carcinoma: an ultrarapid detection system for intraperitoneal Free cancer cells and a prophylactic strategy for peritoneal metastasis. Clin Cancer Res. 2003;9(2):678-85. [ Links ]

65. Miyagawa K, Sakakura C, Nakashima S, Yoshikawa T, Fukuda K, Kin S, et al. Overexpression of RegIV in peritoneal dissemination of gastric cancer and its potential as A novel marker for the detection of peritoneal micrometastasis. Anticancer Res. 2008;28(2B):1169-79. [ Links ]

66. Miyashiro I, Takachi K, Doki Y, Ishikawa O, Ohigashi H, Murata K, et al. When is curative gastrectomy justified for gastric cancer with positive peritoneal lavage cytology but negative macroscopic peritoneal implant? World J Surg. 2005;29(9):1131-4, http://dx.doi.org/10.1007/s00268-005-7703-6. [ Links ]

67. Nakagawa S, Nashimoto A, Yabusaki H. Role of staging laparoscopy with peritoneal lavage cytology in the treatment of locally advanced gastric cancer. Gastric Cancer. 2007;10(1):29-34, http://dx.doi.org/10.1007/s10120-006-0406-3. [ Links ]

68. Nakagohri T, Yoneyama Y, Kinoshita T, Konishi M, Inoue K, Takahashi S. Prognostic significance of peritoneal washing cytology in patients with potentially resectable gastric cancer. Hepato Gastroenterol. 2008;55(86-87):1913-5. [ Links ]

69. Nakajima T, Harashima S, Hirata M, Kajitani T. Prognostic and therapeutic values of peritoneal cytology in gastric cancer. Acta Cytol. 1978;22(4):225-9. [ Links ]

70. Nakanishi H, Kodera Y, Yamamura Y, Ito S, Kato T, Ezaki T, et al. Rapid quantitative detection of carcinoembryonic antigen-expressing free tumor cells in the peritoneal cavity of gastric-cancer patients with real-time RT-PCR on the LightCycler. Int J Cancer. 2000;89(5):411-7, http://dx.doi.org/10.1002/1097-0215(20000920)89:5<411::AID-IJC3>3.0.CO;2-5. [ Links ]

71. Nakanishi H, Kodera Y, Yamamura Y, Kuzuya K, Nakanishi T, Ezaki T, et al. Molecular diagnostic detection of Free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies. Cancer Chemother Pharmacol. 1999;43 Suppl:S32-6, http://dx.doi.org/10.1007/s002800050869. [ Links ]

72. Nekarda H, Gess C, Stark M, Mueller JD, Fink U, Schenck U, et al. Immunocytochemically detected free peritoneal tumour cells (FPTC) are a strong prognostic factor in gastric carcinoma. Br J Cancer. 1999;79(3-4):611-9, http://dx.doi.org/10.1038/sj.bjc.6690096. [ Links ]

73. Nishiyama M, Takashima I, Tanaka T, Yoshida K, Toge T, Nagata N, et al. Carcinoembryonic antigen levels in the peritoneal cavity: useful guide to peritoneal recurrence and prognosis for gastric cancer. World J Surg. 1995;19(1):133-7, http://dx.doi.org/10.1007/BF00316997. [ Links ]

74. Nishizawa M, Seshimo A, Miyake K, Amano K, Kameoka S. Usefulness of the TRC method in the peritoneal washing cytology for gastric cancer. Hepatogastroenterology. 2014;61(129):240-4. [ Links ]

75. Oh CA, Bae JM, Oh SJ, Choi MG, Noh JH, Sohn TS, et al. Long-term results and prognostic factors of gastric cancer patients with only positive peritoneal lavage cytology. J Surg Oncol. 2012;105(4):393-9, http://dx.doi.org/10.1002/jso.22091. [ Links ]

76. Ohashi N, Nakanishi H, Kodera Y, Ito S, Mochizuki Y, Koike M, et al. Intraoperative quantitative detection of CEA mRNA in the peritoneal lavage of gastric cancer patients with transcription reverse-transcription concerted (TRC) method. A comparative study with real-time quantitative RT-PCR. Anticancer Res. 2007;27(4C):2769-77. [ Links ]

77. Oyama K, Terashima M, Takagane A, Maesawa C. Prognostic significance of peritoneal minimal residual disease in gastric cancer detected by reverse transcription-polymerase chain reaction. Br J Surg. 2004;91(4):435-43, http://dx.doi.org/10.1002/bjs.4455. [ Links ]

78. Ozer I, Bostanci EB, Dalgic T, Karaman K, Ulas M, Ozogul YB, et al. Presence of free cancer cells in the peritoneal cavity of patients who underwent curative gastrectomy with lymph node dissection. Hepatogastroenterology. 2012;59(117):1657-60, http://dx.doi.org/10.5754/hge11562. [ Links ]

79. Ribeiro U Jr, Gama-Rodrigues JJ, Safatle-Ribeiro AV, Bitelman B, Ibrahim RE, Ferreira MB, et al. Prognostic significance of intraperitoneal free cancer cells obtained by laparoscopic peritoneal lavage in patients with gastric cancer. J Gastrointest Surg. 1998;2(3):244-9, http://dx.doi.org/10.1016/S1091-255X(98)80019-X. [ Links ]

80. Rosenberg R, Nekarda H, Bauer P, Schenck U, Hoefler H, Siewert JR. Free peritoneal tumour cells are an independent prognostic factor in curatively resected stage IB gastric carcinoma. Br J Surg. 2006;93(3):325-31, http://dx.doi.org/10.1002/bjs.5196. [ Links ]

81. Ryu CK, Park JI, Min JS, Jin SH, Park SH, Bang HY, et al. The Clinical Significance and Detection of Intraperitoneal Micrometastases by ThinPrep(R) Cytology with Peritoneal Lavage Fluid in Patients with Advanced Gastric Cancer. J Korean Gastric Cancer Assoc. 2008;8(4):189-97. [ Links ]

82. Saito H, Kihara K, Kuroda H, Matsunaga T, Tatebe S, Ikeguchi M. Surgical outcomes for gastric cancer patients with intraperitoneal free cancer cell, but no macroscopic peritoneal metastasis. J Surg Oncol. 2011;104(5):534-7, http://dx.doi.org/10.1002/jso.21983. [ Links ]

83. Sakakura C, Hagiwara A, Shirasu M, Yasuoka R, Fujita Y, Nakanishi M, et al. Polymerase chain reaction for detection of carcinoembryonic antigen-expressing tumor cells on milky spots of the greater omentum in gastric cancer patients: a pilot study. Int J Cancer. 2001;95(5):286-9, http://dx.doi.org/10.1002/1097-0215(20010920)95:5<286::AID-IJC1049>3.0.CO;2-Q. [ Links ]

84. Schott A, Vogel I, Krueger U, Kalthoff H, Schreiber HW, Schmiegel W, et al. Isolated tumor cells are frequently detectable in the peritoneal cavity of gastric and colorectal cancer patients and serve as a new prognostic marker. Ann Surg. 1998;227(3):372-9, http://dx.doi.org/10.1097/00000658-199803000-00009. [ Links ]

85. Song KY, Kim JJ, Kim SN, Park CH. Staging laparoscopy for advanced gastric cancer: is it also useful for the group which has an aggressive surgical strategy? World J Surg. 2007;31(6):1228-3, http://dx.doi.org/10.1007/s00268-007-9017-3. [ Links ]

86. Suzuki O, Fukuchi M, Mochiki E, Ishiguro T, Sobajima J, Onozawa H, et al. Prognostic role of gastrectomy in patients with gastric cancer with positive peritoneal cytology. Int Surg. 2014;99(6):830-4, http://dx.doi.org/10.9738/INTSURG-D-14-00119.1. [ Links ]

87. Suzuki T, Ochiai T, Hayashi H, Hori S, Shimada H, Isono K. Peritoneal lavage cytology findings as prognostic factor for gastric cancer. Semin Surg Oncol. 1999;17(2):103-7, http://dx.doi.org/10.1002/(SICI)1098-2388(199909)17:2<103::AID-SSU4>3.0.CO;2-Q. [ Links ]

88. Takata A, Kurokawa Y, Fujiwara Y, Nakamura Y, Takahashi T, Yamasaki M, et al. Prognostic value of CEA and CK20 mRNA in the peritoneal lavage fluid of patients undergoing curative surgery for gastric cancer. World J Surg. 2014;38(5):1107-11, http://dx.doi.org/10.1007/s00268-013-2385-y. [ Links ]

89. Tamura N, Iinuma H, Takada T. Prospective study of the quantitative carcinoembryonic antigen and cytokeratin 20 mRNA detection in peritoneal washes to predict peritoneal recurrence in gastric carcinoma patients. Oncol Rep. 2007;17(3):667-72. [ Links ]

90. Tamura S, Fujiwara Y, Kimura Y, Fujita J, Imamura H, Kinuta M, et al. Prognostic information derived from RT-PCR analysis of peritoneal fluid in gastric cancer patients: results from a prospective multicenter clinical trial. J Surg Oncol. 2014;109(2):75-80, http://dx.doi.org/10.1002/jso.23472. [ Links ]

91. Tourani SS, Cabalag C, Link E, Chan ST, Duong CP. Laparoscopy and peritoneal cytology: important prognostic tools to guide treatment selection in gastric adenocarcinoma. ANZ J Surg. 2015;85(1-2):69-73, http://dx.doi.org/10.1111/ans.12197. [ Links ]

92. Vogel P, Rüschoff J, Kümmel S, Zirngibl H, Hofstädter F, Hohenberger W, et al. Immunocytology improves prognostic impact of peritoneal tumour cell detection compared to conventional cytology in gastric cancer. Eur J Surg Oncol. 1999;25(5):515-9, http://dx.doi.org/10.1053/ejso.1999.0688. [ Links ]

93. Wang JY, Lin SR, Lu CY, Chen CC, Wu DC, Chai CY, et al. Gastric cancer cell detection in peritoneal lavage: RT-PCR for carcinoembryonic antigen transcripts versus the combined cytology with peritoneal carcinoembryonic antigen levels. Cancer Lett. 2005;223(1):129-35, http://dx.doi.org/10.1016/j.canlet.2004.09.031. [ Links ]

94. Wong J, Kelly KJ, Mittra A, Gonen M, Allen P, Fong Y, et al. RT-PCR increases detection of submicroscopic peritoneal metastases in gastric cancer and has prognostic significance. J Gastrointest Surg. 2012;16(5):889-96, http://dx.doi.org/10.1007/s11605-012-1845-2. [ Links ]

95. Wu CC, Chen JT, Chang MC, Ho WL, Chen CY, Yeh DC, et al. Optimal surgical strategy for potentially curable serosa-involved gastric carcinoma with intraperitoneal free cancer cells. J Am Coll Surg. 1997;184(6):611-7. [ Links ]

96. Yamamoto M, Matsuyama A, Kameyama T, Okamoto M, Okazaki J, Utsunomiya T, et al. Prognostic re-evaluation of peritoneal lavage cytology in Japanese patients with gastric carcinoma. Hepatogastroenterology. 2009;56(89):261-5. [ Links ]

97. Yamamoto M, Yoshinaga K, Matsuyama A, Tsutsui S, Ishida T. CEA/CA72-4 levels in peritoneal lavage fluid are predictive factors in patients with gastric carcinoma. J Cancer Res Clin Oncol. 2014;140(4):607-12, http://dx.doi.org/10.1007/s00432-014-1601-y. [ Links ]

98. Yamamoto M, Baba H, Kakeji Y, Endo K, Ikeda Y, Toh Y, et al. Prognostic significance of tumor markers in peritoneal lavage in advanced gastric cancer. Oncology. 2004;67(1):19-26, http://dx.doi.org/10.1159/000080281. [ Links ]

99. Yamashita K, Sakuramoto S, Kikuchi S, Katada N, Kobayashi N, Watanabe M. Strong association of lymph node metastasis with intraperitoneal free cancer cell (IFCC) in advanced gastric cancer. Hepatogastroenterology. 2008;55(86-87):1873-7. [ Links ]

100. Yoneda A, Taniguchi K, Torashima Y, Susumu S, Kanetaka K, Kuroki T, et al. The detection of gastric cancer cells in intraoperative peritoneal lavage using the reverse transcription-loop-mediated isothermal amplification method. J Surg Res. 2014;187(1):e1-6, http://dx.doi.org/10.1016/j.jss.2013.01.001. [ Links ]

101. Yonemura Y, Endou Y, Fujimura T, Fushida S, Bandou E, Kinoshita K, et al. Diagnostic value of preoperative RT-PCR-based screening method to detect carcinoembryonic antigen-expressing free cancer cells in the peritoneal cavity from patients with gastric cancer. ANZ J Surg. 2001;71(9):521-8, http://dx.doi.org/10.1046/j.1440-1622.2001.02187.x. [ Links ]

102. Yonemura Y, Fujimura T, Ninomiya I, Kim BS, Bandou E, Sawa T, et al. Prediction of peritoneal micrometastasis by peritoneal lavaged cytology and reverse transcriptase-polymerase chain reaction for matrix metalloproteinase-7 mRNA. Clin Cancer Res. 2001;7(6):1647-53. [ Links ]

103. Yoshikawa T, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H, Noguchi Y. Peritoneal cytology in patients with gastric cancer exposed to the serosa--a proposed new classification based on the local and distant cytology. Hepatogastroenterology. 2003;50(52):1183-6. [ Links ]

104. Zhang YS, Xu J, Luo GH, Wang RC, Zhu J, Zhang XY, et al. Detection of carcinoembryonic antigen mRNA in peritoneal washes from gastric cancer patients and its clinical significance. World J Gastroenterol. 2006;12(9):1408-11, http://dx.doi.org/10.3748/wjg.v12.i9.1408. [ Links ]

105. Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Morrow M (eds). AJCC Cancer Staging Manual. 6th ed.. New York: Springer-Verlag; 2002. [ Links ]

106. Pecqueux M, Fritzmann J, Adamu M, Thorlund K, Kahlert C, Reißfelder C, et al. Free intraperitoneal tumor cells and outcome in gastric cancer patients: a systematic review and meta-analysis. Oncotarget. 2015;6(34):35564-78, http://dx.doi.org/10.18632/oncotarget.5595. [ Links ]

107. Maehara Y, Tomisaki S, Oda S, Sakaguchi Y, Ichiyoshi Y, Sugimachi K. Lymphatic advancement to peritoneal dissemination and liver metastasis in gastric cancer patients. Anticancer Res. 1994;14(6B):2755-7. [ Links ]

108. Kusamura S, Baratti D, Zaffaroni N, Villa R, Laterza B, Balestra MR, et al. Pathophysiology and biology of peritoneal carcinomatosis. World J Gastrointest Oncol. 2010;2(1):12-8, http://dx.doi.org/10.4251/wjgo.v2.i1.12. [ Links ]

Received: July 23, 2016; Revised: August 29, 2016; Accepted: September 9, 2016

E-mail: franciscotustumi@gmail.com

No potential conflict of interest was reported.

Tustumi F was responsible for the elaboration of the project and manuscript writing. Bernardo WM was responsible for the statistical analysis. Dias AR and Ramos MF helped with manuscript revision. Cecconello I and Zilberstein B selected the articles. Ribeiro-Junior U was responsible for the elaboration of the project.

Creative Commons License This is an Open Access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.