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Surgical Endoscopy

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01-07-2004 | Original article

Port-site metastasis after CO₂ pneumoperitoneum

Role of adhesion molecules and prevention with antiadhesion molecules

Authors: Y. Hirabayashi, K. Yamaguchi, N. Shiraishi, Y. Adachi, I. Saiki, S. Kitano

Published in: Surgical Endoscopy | Issue 7/2004

Abstract

Background

Port-site metastasis is a continuing problem in laparoscopic cancer surgery. To clarify the role of adhesion molecules in the development of port-site metastasis, particularly with regard to prevention, we performed experiments in which port-site metastasis was inhibited using antibodies against extracellular matrix proteins or the active Arg–Gly–Asp (RGD) peptide after CO₂ pneumoperitoneum in a murine model.

Methods

We examined the development of port-site metastasis under the following conditions: (1) CO₂ pneumoperitoneum with or without hyaluronic acid and anti-integrin or anti-CD44 antibody and (2) CO₂ pneumoperitoneum and a RGD peptide or pseudo-RGD sequence peptide (FC-336). BALB/c mice (n = 130) were injected with 5 × 10⁵ human gastric cancer cells (MKN45) and either antibody or peptide, treated with CO₂ pneumoperitoneum, and injected intraperitoneally with antibody or peptide for 5 days. Three weeks after CO₂ pneumoperitoneum, the frequency and weight of port-site metastatic tumors were determined.

Results

Anti-integrin antibody significantly decreased the weight of port-site metastatic tumors without hyaluronic acid (control vs anti-integrin: 8.2 ± 7.1 vs 3.6 ± 4.5 mg; p < 0.05) but not the frequency of port-site metastases. With hyaluronic acid, the frequency of port-site metastasis and the weight of port-site metastatic tumors were significantly decreased both by anti-integrin and by anti-CD44 antibody (control vs anti-integrin and anti-CD44; 95% and 8.5 ± 7.2 mg vs 50% and 3.1 ± 4.3 mg and 55% and 3.3 ± 5.1 mg, respectively; p < 0.05). RGD peptide and FC-336 also inhibited port-site metastasis in a dose-dependent manner.

Conclusion

Cell adhesion molecules integrin and CD44 play an important role in the development of port-site metastasis after laparoscopic cancer surgery. Intraperitoneal injection of RGD peptide or pseudo-RGD sequence peptide (FC-336) can prevent port-site metastasis.

Adachi, Y, Shiraishi, N, Shiromizu, A, Bandoh, T, Aramaki, M, Kitano, S 2000Laparoscopy-assisted Billroth I gastrectomy compared with conventional open gastrectomy.Arch Surg135806810CrossRefPubMed

Aoki, Y, Shimura, H, Li, H, Mizumoto, K, Date, K, Tanaka, M 1999A model of port-site metastases of gallbladder cancer: the influence of peritoneal injury and its repair on abdominal wall metastases.Surgery125553559CrossRefPubMed

Chekan, EG, Nataraj, C, Clary, EM, Hayward, TZ, Brody, FJ, Stamat, JC, Fina, MC, Eubanks, WS, Westcott, CJ 1999Intraperitoneal immunity and pneumoperitoneum.Surg Endosc1311351138CrossRefPubMed

Fujii, H, Inobe, M, Hayakawa, Y, Kimura, F, Murakami, M, Onishi, Y, Azuma, I, Uede, T, Saiki, I 1998Vaccination with B7-1⁺ tumor and anti-adhesion therapy with RGD pseudo-peptide (FC-336) efficiently induce anti-metastatic effect.Clin Exp Metastasis16141148CrossRefPubMed

Fujii, H, Nishikawa, N, Komazawa, H, Suzuki, M, Kojima, M, Itoh, I, Obata, A, Ayukawa, K, Azuma, I, Saiki, I 1998A new pseudo-peptide of Arg–Gly–Asp (RGD) with inhibitory effect on tumor metastasis and enzymatic degradation of extracellular matrix.Clin Exp Metastasis1694104PubMed

Hartley, JE, Mehigan, BJ, MacDonald, AW, Lee, PW, Monson, JR 2000Patterns of recurrence and survival after laparoscopic and conventional resections for colorectal carcinoma.Ann Surg232181186CrossRefPubMed

Hewett, PJ, Thomas, WM, King, G, Eaton, M 1996Intraperitoneal cell movement during abdominal carbon dioxide insufflation and laparoscopy. An in vivo model.Dis Colon Rectum396266

Hirabayashi, Y, Yamaguchi, K, Shiraishi, N, Adachi, Y, Kitamura, K, Kitano, S 2002Development of port-site metastasis after pneumoperitoneum: a scanning electron microscopy study.Surg Endosc16864868CrossRefPubMed

Jacobi, CA, Ordemann, J, Bohm, B, Zieren, HU, Sabat, R, Muller, JM 1997Inhibition of peritoneal tumor cell growth and implantation in laparoscopic surgery in a rat model.Am J Surg174359363CrossRefPubMed

10.

Kitano, S, Shimoda, K, Miyahara, M, Shiraishi, N, Bandoh, T, Yoshida, T, Shuto, K, Kobayashi, M 1995Laparoscopic approaches in the management of patients with early gastric carcinomas.Surg Laparosc Endosc5359362PubMed

11.

Neuhaus, SJ, Texler, M, Hewett, PJ, Watson, DI 1998Port-site metastases following laparoscopic surgery.Br J Surg85735741CrossRefPubMed

12.

Neuhaus, SJ, Watson, DI, Ellis, T, Rofe, AM, Jamieson, GG 1999Influence of cytotoxic agents on intraperitoneal tumor implantation after laparoscopy.Dis Colon Rectum421015PubMed

13.

Nishimura, S, Chung, YS, Yashiro, M, Inoue, T, Sowa, M 1996CD44H plays an important role in peritoneal dissemination of scirrhous gastric cancer cell.Jpn J Cancer Res8712351244PubMed

14.

Ohnishi, Y, Fujii, H, Murakami, K, Sakamoto, T, Tsukada, K, Fujimaki, M, Kojima, M, Saiki, I 1998A new pseudo-peptide analogue of Arg–Gly–Asp (RGD) sequence inhibits liver metastasis of colon 26-L5 carcinoma cells.Cancer Lett124157163CrossRefPubMed

15 .

Schaeff, B, Paolucci, V, Thomopoulos, J 1998Port site recurrences after laparoscopic surgery.Dig Surg15124134CrossRefPubMed

16.

Suematsu, T, Shiromizu, A, Yamaguchi, K, Shiraishi, N, Adachi, Y, Kitano, S 1999Convenient murine pneumoperitoneal model for study of laparoscopic cancer surgery.Surg Laparosc Endosc9279281CrossRef

17.

Strobel, T, Swanson, L, Cannistra, SA 1997In vivo inhibition of CD44 limits intra-abdominal spread of a human ovarian cancer xenograft in nude mice: a novel role for CD44 in the process of peritoneal implantation.Cancer Res5712281232PubMed

18.

Wexner, SD, Cohen, SM 1995Port site metastases after laparoscopic colorectal surgery for cure of malignancy.Br J Surg82295298PubMed

19.

Yamaguchi, K, Hirabayashi, Y, Shiromizu, A, Shiraishi, N, Adachi, Y, Kitano, S 2001Enhancement of port site metastasis by hyaluronic acid under CO₂ pneumoperitoneum in a murine model.Surg Endosc15504507CrossRefPubMed

20.

Yamaguchi, K, Hirabayashi, Y, Suematsu, T, Shiraishi, N, Adachi, Y, Kitano, S 2001Hyaluronic acid secretion during carbon dioxide pneumoperitoneum and its association with port-site metastasis in a murine model.Surg Endosc155962CrossRefPubMed

21.

Yun, Z, Menter, DG, Nicolson, GL 1996Involvement of integrin α_v β₃ in cell adhesion, motility, and liver metastasis of murine RAW117 large cell lymphoma.Cancer Res5631033111PubMed

Title: Port-site metastasis after CO2 pneumoperitoneum
Role of adhesion molecules and prevention with antiadhesion molecules
Authors: Y. Hirabayashi
K. Yamaguchi
N. Shiraishi
Y. Adachi
I. Saiki
S. Kitano
Publication date: 01-07-2004
Publisher: Springer-Verlag
Published in: Surgical Endoscopy / Issue 7/2004
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI: https://doi.org/10.1007/s00464-003-9150-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Port-site metastasis after CO₂ pneumoperitoneum

Role of adhesion molecules and prevention with antiadhesion molecules

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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