Surgery-induced peritoneal cancer cells in patients who have undergone curative gastrectomy for gastric cancer.
BACKGROUND
Some patients who undergo curative gastrectomy with lymph node dissection (LND) for gastric cancer (GC) show subsequent peritoneal metastasis. The source of these metastatic cells remains unclear.


METHODS
Curative gastrectomy with LND was performed in 102 patients with GC. Peritoneal washing was collected before and after gastrectomy. Cytology, reverse transcription-polymerase chain reaction, and cell culture were used to determine the presence of cancer cells. The proliferative potential of tumor cells was evaluated using Ki-67 staining. Tumorigenic capacity was assessed by cell injection into the peritoneal cavity of NOD/ShiJic-scid mice. Peritoneal recurrence-free survival (RFS) and peritoneal recurrence rate (RR) were examined to determine the clinical relevance of detected cancer cells.


RESULTS
Of 102 peritoneal washing samples obtained before gastrectomy, 57 showed no CEA or CK20 mRNA amplification. After gastrectomy, CEA or CK20 mRNA was detected in 35 of these 57 samples, and viable cancer cells were identified in 24. The viable cancer cells in all 24 cases showed Ki-67 positivity, indicating proliferative activity. Cultured viable cancer cells generated peritoneal nodules after spilling over the peritoneal cavity in NOD/ShiJic-scid mice in 4 cases. The peritoneal RFS of patients with CEA or CK20 mRNA amplification after gastrectomy was significantly poorer than that of patients with negative amplification (p < .05). The 24 patients with viable cancer cells in the peritoneal cavity after gastrectomy showed higher peritoneal RR than those without them (p = .033).


CONCLUSIONS
Viable tumorigenic cancer cells spilled into the peritoneal cavity during surgery, indicating that surgery induces peritoneal metastasis.
Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
Katsushi
K
Takebayashi
Satoshi
S
Murata
Hiroshi
H
Yamamoto
Mitsuaki
M
Ishida
Tsuyoshi
T
Yamaguchi
Masatsugu
M
Kojima
Tomoharu
T
Shimizu
Hisanori
H
Shiomi
Hiromichi
H
Sonoda
Shigeyuki
S
Naka
Eiji
E
Mekata
Hidetoshi
H
Okabe
Tohru
T
Tani
D000230:Adenocarcinoma / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry / Q000473:pathology*; D002272:Carcinoembryonic Antigen / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D018572:Disease-Free Survival; D005260:Female; D005743:Gastrectomy / Q000009:adverse effects*; D006801:Humans; D053554:Keratin-20 / Q000235:genetics; D008197:Lymph Node Excision / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009366:Neoplasm Seeding; D010533:Peritoneal Lavage; D010534:Peritoneal Neoplasms / Q000473:pathology* / Q000556:secondary*; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000601:surgery*; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D053554:Keratin-20; D012333:RNA, Messenger