Skip to main content
Top
Published in: Annals of Surgical Oncology 6/2014

01-06-2014 | Gastrointestinal Oncology

Surgery-Induced Peritoneal Cancer Cells in Patients Who Have Undergone Curative Gastrectomy for Gastric Cancer

Authors: Katsushi Takebayashi, MD, Satoshi Murata, MD, Hiroshi Yamamoto, MD, Mitsuaki Ishida, PhD, Tsuyoshi Yamaguchi, MD, Masatsugu Kojima, MD, Tomoharu Shimizu, MD, Hisanori Shiomi, MD, Hiromichi Sonoda, MD, Shigeyuki Naka, MD, Eiji Mekata, MD, Hidetoshi Okabe, PhD, Tohru Tani, MD

Published in: Annals of Surgical Oncology | Issue 6/2014

Login to get access

Abstract

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.
Literature
1.
go back to reference Wu CW, Hsiung CA, Lo SS, et al. Nodal dissection for patients with gastric cancer: a randomised controlled trial. Lancet Oncol. 2006;7:309–15.PubMedCrossRef Wu CW, Hsiung CA, Lo SS, et al. Nodal dissection for patients with gastric cancer: a randomised controlled trial. Lancet Oncol. 2006;7:309–15.PubMedCrossRef
2.
go back to reference Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.PubMedCrossRef Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.PubMedCrossRef
4.
go back to reference Yoo CH, Noh SH, Shin DW, et al. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87:236–42.PubMedCrossRef Yoo CH, Noh SH, Shin DW, et al. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87:236–42.PubMedCrossRef
5.
go back to reference Kitamura Y, Hayashi K, Sasagawa T, et al. Pilot study of S-1 in patients with disseminated gastric cancer. Drugs Exp Clin Res. 2003;29:125–30.PubMed Kitamura Y, Hayashi K, Sasagawa T, et al. Pilot study of S-1 in patients with disseminated gastric cancer. Drugs Exp Clin Res. 2003;29:125–30.PubMed
6.
go back to reference Ribeiro U Jr, Gama-Rodrigues JJ, Safatle-Ribeiro AV, et al. Prognostic significance of intraperitoneal free cancer cells obtained by laparoscopic peritoneal lavage in patients with gastric cancer. J Gastrointest Surg. 1998;2:244–9.PubMedCrossRef Ribeiro U Jr, Gama-Rodrigues JJ, Safatle-Ribeiro AV, et al. Prognostic significance of intraperitoneal free cancer cells obtained by laparoscopic peritoneal lavage in patients with gastric cancer. J Gastrointest Surg. 1998;2:244–9.PubMedCrossRef
7.
go back to reference Moriguchi S, Maehara Y, Korenaga D, et al. Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer. Surg Oncol. 1992;1:341–6.PubMedCrossRef Moriguchi S, Maehara Y, Korenaga D, et al. Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer. Surg Oncol. 1992;1:341–6.PubMedCrossRef
8.
go back to reference Ikeguchi M, Oka A, Tsujitani S, et al. Relationship between area of serosal invasion and intraperitoneal free cancer cells in patients with gastric cancer. Anticancer Res. 1994;14:2131–4.PubMed Ikeguchi M, Oka A, Tsujitani S, et al. Relationship between area of serosal invasion and intraperitoneal free cancer cells in patients with gastric cancer. Anticancer Res. 1994;14:2131–4.PubMed
9.
go back to reference Shimada S, Yagi Y, Shiomori K, et al. Characterization of early gastric cancer and proposal of optimal therapeutic strategy. Surgery. 2001;129:714–9.PubMedCrossRef Shimada S, Yagi Y, Shiomori K, et al. Characterization of early gastric cancer and proposal of optimal therapeutic strategy. Surgery. 2001;129:714–9.PubMedCrossRef
10.
go back to reference Bando E, Yonemura Y, Takeshita Y, et al. Intraoperative lavage for cytological examination in 1297 patients with gastric carcinoma. Am J Surg. 1999;178:256–62.PubMedCrossRef Bando E, Yonemura Y, Takeshita Y, et al. Intraoperative lavage for cytological examination in 1297 patients with gastric carcinoma. Am J Surg. 1999;178:256–62.PubMedCrossRef
11.
go back to reference Boku T, Nakane Y, Minoura T, et al. Prognostic significance of serosal invasion and free intraperitoneal cancer cells in gastric cancer. Br J Surg. 1990;77:436–9.PubMedCrossRef Boku T, Nakane Y, Minoura T, et al. Prognostic significance of serosal invasion and free intraperitoneal cancer cells in gastric cancer. Br J Surg. 1990;77:436–9.PubMedCrossRef
12.
go back to reference Marutsuka T, Shimada S, Shiomori K, 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;9:678–85.PubMed Marutsuka T, Shimada S, Shiomori K, 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;9:678–85.PubMed
13.
go back to reference Fink A, Longmire W. Carcinoma of stomach. In: Subiston DC, ed. Textbook of surgery. 14th ed. Philadelphia: WB Saunders; 1991:814–27. Fink A, Longmire W. Carcinoma of stomach. In: Subiston DC, ed. Textbook of surgery. 14th ed. Philadelphia: WB Saunders; 1991:814–27.
14.
go back to reference Ribeiro U Jr, Safatle-Ribeiro AV, Zilberstein B, et al. Does the intraoperative peritoneal lavage cytology add prognostic information in patients with potentially curative gastric resection? J Gastrointest Surg. 2006;10:170–6.PubMedCrossRef Ribeiro U Jr, Safatle-Ribeiro AV, Zilberstein B, et al. Does the intraoperative peritoneal lavage cytology add prognostic information in patients with potentially curative gastric resection? J Gastrointest Surg. 2006;10:170–6.PubMedCrossRef
15.
go back to reference Han TS, Kong SH, Lee HJ, et al. Dissemination of free cancer cells from the gastric lumen and from perigastric lymphovascular pedicles during radical gastric cancer surgery. Ann Surg Oncol. 2011;18:2818–25.PubMedCrossRef Han TS, Kong SH, Lee HJ, et al. Dissemination of free cancer cells from the gastric lumen and from perigastric lymphovascular pedicles during radical gastric cancer surgery. Ann Surg Oncol. 2011;18:2818–25.PubMedCrossRef
16.
go back to reference Japanese Research Society for Gastric Cancer. Japanese Classification of Gastric Carcinoma. 2nd ed. Tokyo: Kanehara; 1998. Japanese Research Society for Gastric Cancer. Japanese Classification of Gastric Carcinoma. 2nd ed. Tokyo: Kanehara; 1998.
17.
go back to reference Kodera Y, Nakanishi H, Ito S, 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;8:142–8.PubMedCrossRef Kodera Y, Nakanishi H, Ito S, 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;8:142–8.PubMedCrossRef
18.
go back to reference 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;17:667–72.PubMed 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;17:667–72.PubMed
19.
go back to reference Mori K, Aoyagi K, Ueda T, et al. Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings. Biochem Biophys Res Commun. 2004;313:931–7.PubMedCrossRef Mori K, Aoyagi K, Ueda T, et al. Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings. Biochem Biophys Res Commun. 2004;313:931–7.PubMedCrossRef
20.
go back to reference van der Bij GJ, Oosterling SJ, Beelen RH, et al. The perioperative period is an underutilized window of therapeutic opportunity in patients with colorectal cancer. Ann Surg. 2009;249:727–34.PubMedCrossRef van der Bij GJ, Oosterling SJ, Beelen RH, et al. The perioperative period is an underutilized window of therapeutic opportunity in patients with colorectal cancer. Ann Surg. 2009;249:727–34.PubMedCrossRef
21.
go back to reference van der Bij GJ, Oosterling SJ, Bögels M, et al. Blocking alpha2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth. Hepatology. 2008;47:532–43.PubMed van der Bij GJ, Oosterling SJ, Bögels M, et al. Blocking alpha2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth. Hepatology. 2008;47:532–43.PubMed
22.
go back to reference Li F, Tiede B, Massagué J, et al. Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res. 2007;17:3–14.PubMedCrossRef Li F, Tiede B, Massagué J, et al. Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res. 2007;17:3–14.PubMedCrossRef
23.
go back to reference Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.PubMedCrossRef Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.PubMedCrossRef
24.
go back to reference Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796:75–90.PubMed Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796:75–90.PubMed
25.
26.
go back to reference Takebayashi K, Shiomi H, Naka S, et al. Utility of a microwave surgical instrument in sealing lymphatic vessels. Am J Surg. 2013;206:229–33.PubMedCrossRef Takebayashi K, Shiomi H, Naka S, et al. Utility of a microwave surgical instrument in sealing lymphatic vessels. Am J Surg. 2013;206:229–33.PubMedCrossRef
27.
go back to reference Tsimoyiannis EC, Jabarin M, Tsimoyiannis JC, et al. Ultrasonically activated shears in extended lymphadenectomy for gastric cancer. World J Surg. 2002;26:158–61.PubMedCrossRef Tsimoyiannis EC, Jabarin M, Tsimoyiannis JC, et al. Ultrasonically activated shears in extended lymphadenectomy for gastric cancer. World J Surg. 2002;26:158–61.PubMedCrossRef
28.
go back to reference Kuramoto M, Shimada S, Ikeshima S, et al. Extensive intraoperative peritoneal lavage as a standard prophylactic strategy for peritoneal recurrence in patients with gastric carcinoma. Ann Surg. 2009;250:242–6.PubMedCrossRef Kuramoto M, Shimada S, Ikeshima S, et al. Extensive intraoperative peritoneal lavage as a standard prophylactic strategy for peritoneal recurrence in patients with gastric carcinoma. Ann Surg. 2009;250:242–6.PubMedCrossRef
29.
go back to reference Ikeguchi M, Matsumoto S, Yoshioka S, et al. Laparoscopic-assisted intraperitoneal chemotherapy for patients with scirrhous gastric cancer. Chemotherapy. 2005;51:15–20.PubMedCrossRef Ikeguchi M, Matsumoto S, Yoshioka S, et al. Laparoscopic-assisted intraperitoneal chemotherapy for patients with scirrhous gastric cancer. Chemotherapy. 2005;51:15–20.PubMedCrossRef
30.
go back to reference Murata S, Naito H, Yamamoto H, et al. Phase II trial of adjuvant hyperthermic intraperitoneal chemotherapy with three drugs for the prophylactic treatment of carcinomatosis after resection of advanced gastric cancer. J Clin Oncol. 2009 ASCO Annual Meeting Proceedings. 2009;27:15588. Murata S, Naito H, Yamamoto H, et al. Phase II trial of adjuvant hyperthermic intraperitoneal chemotherapy with three drugs for the prophylactic treatment of carcinomatosis after resection of advanced gastric cancer. J Clin Oncol. 2009 ASCO Annual Meeting Proceedings. 2009;27:15588.
Metadata
Title
Surgery-Induced Peritoneal Cancer Cells in Patients Who Have Undergone Curative Gastrectomy for Gastric Cancer
Authors
Katsushi Takebayashi, MD
Satoshi Murata, MD
Hiroshi Yamamoto, MD
Mitsuaki Ishida, PhD
Tsuyoshi Yamaguchi, MD
Masatsugu Kojima, MD
Tomoharu Shimizu, MD
Hisanori Shiomi, MD
Hiromichi Sonoda, MD
Shigeyuki Naka, MD
Eiji Mekata, MD
Hidetoshi Okabe, PhD
Tohru Tani, MD
Publication date
01-06-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 6/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-3525-9

Other articles of this Issue 6/2014

Annals of Surgical Oncology 6/2014 Go to the issue