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Abstract
Background/Aims
Peritoneal micrometastasis is known to play an important role in the recurrence of gastric cancer. However, its effects remain equivocal. Herein, we examine the messenger RNA (mRNA) as tumor markers, carcinoembryonic antigen (CEA), and cytokeratin 20 (CK20), in peritoneal washing fluid. Moreover, we evaluate whether these results could predict the recurrence of gastric cancer following curative resection.
Methods
We prospectively enrolled 132 patients with gastric cancers, who had received an operation, between January 2010 and January 2013. The peritoneal lavage fluid was collected at the operation field and semi-quantitative PCR was performed using the primers for CEA and CK20. We excluded patients with stage IA (n=28) early gastric cancer, positive cytologic examination of peritoneal washings (n=7), and those who were lost during follow up (n=18).
Results
A total of 79 patients with gastric cancers were enrolled, and the mean follow-up period was 39.95±19.25 months (range, 5–72 months). According to the multivariate analysis, T4 stage at the initial diagnosis was significantly associated with recurrence. All cases of recurrence were CEA positive and 6 cases were CK20 positive. The positive and negative predictive values of CEA were 32.0% and 100%, respectively, whereas those of CK20 were 37.5% and 71.4%, respectively. Disease free survival of CK20-negative cases was 36.17±20.28 months and that of CK20-positive cases was 32.06±22.95 months (p=0.39).
References
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Fig. 1.
RT-PCR for mRNA of CEA and CK20. RT-PCR, real time polymerase chain reaction; mRNA, messenger RNA; CEA, carcinoembryonic antigen; CK20, cytokeratin 20; GPADH, glyceraldehyde-3-phosphate dehydrogenase.
Fig. 2.
Kaplan-Meier curve for analyzing DFS between the CK20 negative and positive groups. DFS, disease free survival; CK20, cytokeratin 20; mRNA, messenger RNA.
Table 1.
Clinical Features of Recurrence in the Patients with Gastric Cancers
| Recurrence (n=24) | Non-recurrence (n=55) | p-value | |
|---|---|---|---|
| Age | 62.04±13.43 | 62.53±12.08 | 0.91 |
| Sex (male: female) | 16: 8 | 41: 14 | 0.47 |
| Smoke | 7 | 15 | 0.86 |
| Alcohol drinking | 13 | 31 | 0.86 |
| Body mass index (kg/m2) | 23.96±3.16 | 23.01±3.56 | 0.37 |
| Presence of atrophy | 10 | 30 | 0.29 |
| Lauren classification (Diffuse) | 12 | 24 | 0.60 |
| Differentiation (Poorly differentiated / Signet ring cell cancer) | 15 | 27 | 0.08 |
| Lymphatic invasion | 19 | 25 | <0.01 a |
| Vascular invasion | 12 | 10 | <0.01 a |
| Perineural invasion | 15 | 19 | 0.02 a |
| Number of dissected lymph nodes at operation | 42.75±13.84 | 37.15±15.55 | 0.28 |
| T stage at diagnosis (T4) | 18 | 8 | <0.01 a |
| N stage at diagnosis (N3) | 12 | 7 | <0.01 a |
| Chemotherapy | 24 | 42 | − |
| Positive result of mRNA-CEA in peritoneal washing | 24 | 51 | − |
| Positive result of mRNA-CK20 in peritoneal washing | 6 | 10 | 0.49 |
| Recurrence | |||
| Multiple lesions | 10 | ||
| Lymph node | 11 | ||
| Liver | 5 | ||
| Peritoneum | 6 | ||
| Colon | 3 | ||
| Pancreas | 3 | ||
| Bone | 2 | ||
| Ovary | 2 | ||
| Lung | 1 | ||
| Stoma | 2 |
Table 2.
Multivariate Analysis of the Factors of Recurrence in the Patients with Gastric Cancers
| Sig. | Exp(B) | 95.0% C.I. for EXP(B) | ||
|---|---|---|---|---|
| Lower | Upper | |||
| Positive result of mRNA-CK20 in peritoneal washing | 0.22 | 2.69 | 0.56 | 12.88 |
| Differentiation (poorly differentiated and signet ring cell type) | 0.28 | 0.43 | 0.10 | 1.96 |
| Lymphatic invasion | 0.87 | 1.15 | 0.22 | 6.13 |
| Vascular invasion | 0.27 | 2.51 | 0.48 | 13.02 |
| Perineural invasion | 0.81 | 1.19 | 0.29 | 4.96 |
| T stage at diagnosis (T4) | <0.01 a | 11.79 | 2.23 | 62.21 |
| N stage at diagnosis (N3) | 0.17 | 2.91 | 0.64 | 13.30 |
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