• 川北醫(yī)學(xué)院附屬醫(yī)院普外一科（四川南充 637000）;

目的 　總結(jié)CO2氣腹對(duì)腫瘤細(xì)胞侵襲性的影響以及目前的研究進(jìn)展。
方法 　復(fù)習(xí)國(guó)內(nèi)外該領(lǐng)域的相關(guān)文獻(xiàn)，回顧性總結(jié)CO2氣腹對(duì)腫瘤細(xì)胞侵襲性的影響以及目前的研究狀況。
結(jié)果 　CO2氣腹可能通過(guò)改變間皮細(xì)胞的結(jié)構(gòu)和功能、改變局部微環(huán)境、影響腫瘤細(xì)胞基因的表達(dá)、改變細(xì)胞因子分泌、改變腫瘤細(xì)胞的黏附性等機(jī)理來(lái)影響腫瘤細(xì)胞的侵襲性。
結(jié)論 　CO2氣腹對(duì)腫瘤細(xì)胞的侵襲性確有影響，但其具體機(jī)理還有待更為深入的研究。

引用本文： 腹腔鏡手術(shù),CO氣腹,腫瘤,侵襲力,轉(zhuǎn)移. CO2氣腹對(duì)腫瘤細(xì)胞侵襲性影響的研究進(jìn)展. 中國(guó)普外基礎(chǔ)與臨床雜志, 2012, 19(12): 1362-1367. doi: 復(fù)制

1. Bracale U， Barone M， Pema F， et al. Laparascopic colon resection for cancer：evidence based results[J]. Acta Chir Iugosl， 2010， 57(3)：37-40.
2. Mareel M， Leroy A. Clinical， cellular， and molecular aspects of cancer invasion[J]. Physiol Rev， 2003， 83(2)：337-376.
3. Griffiths JR， McIntyre DJ， Howe FA，et al. Why are cancers acidic? A carrier-mediated diffusion model for H＋ transport in the interstitial ?uid[J]. Novartis Found Symp， 2001， 240：46-62.
4. Paget S. The distribution of secondary growths in cancer of the breast. 1889[J]. Cancer Metastasis Rev， 1989， 8(2)：98-101.
5. Lackey LW， Ott DE. Terminal gas velocity during laparoscopy[J]. J Am Assoc Gynecol Laparosc， 2002， 9(3)：297-305.
6. Ott DE. Desertification of the peritoneum by thin-film evaporationduring laparoscopy[J]. JSLS， 2003， 7(3)：189-195.
7. Verguts J， Vergote I， Amant F， et al. The addition of 4% oxygen to the CO2 pneumoperitoneum does not decrease dramatically port site metastases[J]. J Minim Invasive Gynecol， 2008， 15(6)：700-703.
8. Reismann M， Wehrmann F， Schukfeh N， et al. Carbon dioxide，hypoxia and low pH lead to overexpression of c-myc and HMGB-1oncogenes in neuroblastoma cells[J]. Eur J Pediatr Surg， 2009， 19(4)：224-227.
9. Krause P， Bobisch NS， Thelen P， et al. The plasminogen activatorinhibitor system in colon cancer cell lines is influenced by the CO2 pneumoperitoneum[J]. Int J Colorectal Dis， 2011， 26(1)：37-43.
10. Zhou HM， Feng B， Zhao HC， et al. Antitumor effects ofhyperthermic CO2 pneumoperitoneum on human gastric cancer cells[J]. Asian Pac J Cancer Prev， 2012， 13(1)：117-122.
11. Li J， Wang JW， Zheng S， et al. Influences of laparoscopicresection on expressions of metastasis genes in colorectal cancer：report of microarray analysis and literature review[J]. Hepatogastroenterology， 2011， 58(112)：1975-1982.
12. Amin MA， Haas CS， Zhu K， et al. Migration inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src， PI3 kinase， and NFkappaB[J]. Blood， 2006， 107(6)：2252-2261.
13. Mohri Y. Prognostic significance of E-cadherin expression inhuman colorectal cancer tissue[J]. Surg Today， 1997， 27(7)：606-612.
14. Ma JJ， Feng B， Zhang Y， et al. Higher CO2-insufflation pressure inhibits the expression of adhesion molecules and the invasion potential of colon cancer cells[J]. World J Gastroenterol， 2009， 15(22)：2714-2722.
15. Ordemann J， Höflich C， Braumann C， et al. Impact of pneumoperitoneum on expression of E-cadherin， CD44v6 and CD54 (ICAM-1) on HT-29 colon-carcinoma cells[J]. Zentralbl Chir， 2005， 130(5)：405-409.
16. Kim ZG， Mehl C， Lorenz M， et al. Impact of laparoscopic CO2-insufflation on tumor-associated molecules in cultured colorectal cancer cells[J]. Surg Endosc， 2002， 16(8)：1182-1186.
17. Matsuzaki S， Jardon K， Maleysson E， et al. Impact of intraperitoneal pressure of a CO2 pneumoperitoneum on the surgical peritoneal environment[J]. Hum Reprod， 2012， 27(6)：1613-1623.
18. Heel KA， Hall JC. Peritoneal defences and peritoneum-associatedlymphoid tissue[J]. Br J Surg， 1996， 83(8)：1031-1036.
19. Schmidt AI， Reismann M， Kübler JF， et al. Exposure to carbon dioxide and helium reduces in vitro proliferation of pediatrictumor cells[J]. Pediatr Surg Int， 2006， 22(1)：72-77.
20. Kuntz C， Wunsch A， Bödeker C， et al. Effect of pressure and gas type on intraabdominal， subcutaneous， and blood pH inlaparoscopy[J]. Surg Endosc， 2000， 14(4)：367-371.
21. Yavuz Y， Rønning K， Lyng O， et al. Effect of carbon dioxide pneumoperitoneum on tissue blood flow in the peritoneum， rectus abdominis， and diaphragm muscles[J]. Surg Endosc， 2003， 17(10)：1632-1635.
22. Wildbrett P， Oh A， Naundorf D， et al. Impact of laparoscopic gases on peritoneal microenvironment and essential parameters of cell function[J]. Surg Endosc， 2003， 17(1)：78-82.
23. Schlotterbeck H， Greib N， Dow WA， et al. Changes in coretemperature during peritoneal insufflation：comparison of two CO2 humidification devices in pigs[J]. J Surg Res， 2011， 171(2)：427-432.
24. Neuhaus SJ， Watson DI. Pneumoperitoneum and peritonealsurface changes：a review[J]. Surg Endosc， 2004， 18(9)：1316-1322.
25. Whelan RL， Franklin M， Holubar SD， et al. Postoperative cell mediated immune response is better preserved after laparoscopic vs. open colorectal resection in humans[J]. Surg Endosc， 2003， 17(6)：972-978.
26. Gitzelmann CA， Mendoza-Sagaon M， Talamini MA， et al.Cell-mediated immune response is better preserved by laparoscopy than laparotomy[J]. Surgery， 2000， 127(1)：65-71.
27. Wichmann MW， Hüttl TP， Winter H， et al. Immunologicaleffects of laparoscopic vs. open colorectal surgery：a prospective clinical study[J]. Arch Surg， 2005， 140(7)：692-697.
28. Brokelman WJ， Lensvelt M， Borel Rinkes IH， et al. Peritoneal changes due to laparoscopic surgery[J]. Surg Endosc， 2011， 25(1)：1-9.
29. Waiwut P， Shin MS， Inujima A， et al. Gomisin N enhances TNF-α-induced apoptosis via inhibition of the NF-κB and EGFR survival pathways[J]. Mol Cell Biochem， 2011， 350(1-2)：169-175.
30. Amin AT， Shiraishi N， Ninomiya S， et al. Increased mRNA expression of epidermal growth factor receptor， human epidermal receptor， and survivin in human gastric cancer after the surgical stress of laparotomy versus carbon dioxide pneumoperitoneum in a murine model[J]. Surg Endosc， 2010， 24(6)：1427-1433.
31. Tawfik Amin A， Shiraishi N， Ninomiya S， et al. Activation of nuclear factor kappa B and induction of migration inhibitory factor in tumors by surgical stress of laparotomy versus carbon dioxide pneumoperitoneum：an animal experiment[J]. Surg Endosc， 2010， 24(3)：578-583.
32. Machado MC， Coelho AM， Martins JO， et al. CO2 abdominal insufflation decreases local and systemic inflammatory response in experimental acute pancreatitis[J]. Pancreas， 2010， 39(2)：175-181.
33. Yu Y， Kuebler J， Groos S， et al. Carbon dioxide modifies the morphology and function of mesothelial cells and facilitates transepithelial neuroblastoma cell migration[J]. Pediatr Surg Int， 2010， 26(1)：29-36.
34. Fuganti PE， Rodrigues Júnior AJ， Rodrigues CJ， et al. Acomparison of the effects of pneumoperitoneum and laparotomy on natural killer cell mediated cytotoxicity and Walker tumor growth in Wistar rats[J]. Surg Endosc， 2006， 20(12)：1858-1861.
35. Mutsaers SE， Whitaker D， Papadimitriou JM. Changes in the concentration of microvilli on the free surface of healing mesothelium are associated with alterations in surface membrane charge[J]. J Pathol， 1996， 180(3)：333-339.
36. Ryan GB， Grobéty J， Majno G. Mesothelial injury and recovery[J]. Am J Pathol， 1973， 71(1)：93-112.
37. Rosário MT， Ribeiro U Jr， Corbett CE， et al. Does CO2 pneumoperitoneum alter the ultra-structuture of the mesothelium?[J]. J Surg Res， 2006， 133(2)：84-88.
38. Du J， Yu PW， Tang B. Application of stereology to study the effects of pneumoperitoneum on peritoneum[J]. Surg Endosc， 2011， 25(2)：619-627.
39. Yamaguchi K， Hirabayashi Y， Suematsu T， et al. Hyaluronic acid secretion during carbon dioxide pneumoperitoneum and its association with port-site metastasis in a murine model[J]. Surg Endosc， 2001， 15(1)：59-62.
40. Volz J， Köster S， Schaeff B， et al. Laparoscopic surgery：the effects of insufflation gas on tumor-induced lethality in nude mice[J]. Am J Obstet Gynecol， 1998， 178(4)：793-795.
41. Metzelder M， Kuebler J， Shimotakahara A， et al. CO2 pneumoperitoneum increases systemic but not local tumor spread after intraperitoneal murine neuroblastoma spillage in mice[J]. Surg Endosc， 2008， 22(12)：2648-2653.
42. Nestler G， Schulz HU， Tautenhahn J， et al. Effects of theangiogenesis inhibitor angiostatin on the growth of CC531 colon carcinoma cells in vitro and in a laparoscopic animal model of peritoneal carcinomatosis[J]. Int J Colorectal Dis， 2006， 21(4)：314-320.
43. 孫鐵為， 李強(qiáng)， 王鋒. 一次性CO2氣腹環(huán)境下氟尿嘧啶對(duì)大鼠腫瘤細(xì)胞生長(zhǎng)及轉(zhuǎn)移的影響[J]. 中國(guó)普外基礎(chǔ)與臨床雜志， 2009， 16(7)：545-549.
44. Nakada H， Ishida H， Hashimoto D， et al. Influence of different pneumoperitoneal pressures on tumor cell distribution in rats[J]. Surg Endosc， 2005， 19(4)：563-568.
45. Volz J， Volz-Köster S， Kanis S， et al. Modulation of tumor-induced lethality after pneumoperitoneum in a mouse model[J]. Cancer， 2000， 89(2)：262-266.
46. Fondrinier E， Descamps P， Arnaud JP， et al. Carbon dioxidepneumoperitoneum and peritoneal carcinosis：review[J].J Gynecol Obstet Biol Reprod (Paris)， 2002， 31(1)：11-27.
  1. 1. Bracale U， Barone M， Pema F， et al. Laparascopic colon resection for cancer：evidence based results[J]. Acta Chir Iugosl， 2010， 57(3)：37-40.
  2. 2. Mareel M， Leroy A. Clinical， cellular， and molecular aspects of cancer invasion[J]. Physiol Rev， 2003， 83(2)：337-376.
  3. 3. Griffiths JR， McIntyre DJ， Howe FA，et al. Why are cancers acidic? A carrier-mediated diffusion model for H＋ transport in the interstitial ?uid[J]. Novartis Found Symp， 2001， 240：46-62.
  4. 4. Paget S. The distribution of secondary growths in cancer of the breast. 1889[J]. Cancer Metastasis Rev， 1989， 8(2)：98-101.
  5. 5. Lackey LW， Ott DE. Terminal gas velocity during laparoscopy[J]. J Am Assoc Gynecol Laparosc， 2002， 9(3)：297-305.
  6. 6. Ott DE. Desertification of the peritoneum by thin-film evaporationduring laparoscopy[J]. JSLS， 2003， 7(3)：189-195.
  7. 7. Verguts J， Vergote I， Amant F， et al. The addition of 4% oxygen to the CO2 pneumoperitoneum does not decrease dramatically port site metastases[J]. J Minim Invasive Gynecol， 2008， 15(6)：700-703.
  8. 8. Reismann M， Wehrmann F， Schukfeh N， et al. Carbon dioxide，hypoxia and low pH lead to overexpression of c-myc and HMGB-1oncogenes in neuroblastoma cells[J]. Eur J Pediatr Surg， 2009， 19(4)：224-227.
  9. 9. Krause P， Bobisch NS， Thelen P， et al. The plasminogen activatorinhibitor system in colon cancer cell lines is influenced by the CO2 pneumoperitoneum[J]. Int J Colorectal Dis， 2011， 26(1)：37-43.
  10. 10. Zhou HM， Feng B， Zhao HC， et al. Antitumor effects ofhyperthermic CO2 pneumoperitoneum on human gastric cancer cells[J]. Asian Pac J Cancer Prev， 2012， 13(1)：117-122.
  11. 11. Li J， Wang JW， Zheng S， et al. Influences of laparoscopicresection on expressions of metastasis genes in colorectal cancer：report of microarray analysis and literature review[J]. Hepatogastroenterology， 2011， 58(112)：1975-1982.
  12. 12. Amin MA， Haas CS， Zhu K， et al. Migration inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src， PI3 kinase， and NFkappaB[J]. Blood， 2006， 107(6)：2252-2261.
  13. 13. Mohri Y. Prognostic significance of E-cadherin expression inhuman colorectal cancer tissue[J]. Surg Today， 1997， 27(7)：606-612.
  14. 14. Ma JJ， Feng B， Zhang Y， et al. Higher CO2-insufflation pressure inhibits the expression of adhesion molecules and the invasion potential of colon cancer cells[J]. World J Gastroenterol， 2009， 15(22)：2714-2722.
  15. 15. Ordemann J， Höflich C， Braumann C， et al. Impact of pneumoperitoneum on expression of E-cadherin， CD44v6 and CD54 (ICAM-1) on HT-29 colon-carcinoma cells[J]. Zentralbl Chir， 2005， 130(5)：405-409.
  16. 16. Kim ZG， Mehl C， Lorenz M， et al. Impact of laparoscopic CO2-insufflation on tumor-associated molecules in cultured colorectal cancer cells[J]. Surg Endosc， 2002， 16(8)：1182-1186.
  17. 17. Matsuzaki S， Jardon K， Maleysson E， et al. Impact of intraperitoneal pressure of a CO2 pneumoperitoneum on the surgical peritoneal environment[J]. Hum Reprod， 2012， 27(6)：1613-1623.
  18. 18. Heel KA， Hall JC. Peritoneal defences and peritoneum-associatedlymphoid tissue[J]. Br J Surg， 1996， 83(8)：1031-1036.
  19. 19. Schmidt AI， Reismann M， Kübler JF， et al. Exposure to carbon dioxide and helium reduces in vitro proliferation of pediatrictumor cells[J]. Pediatr Surg Int， 2006， 22(1)：72-77.
  20. 20. Kuntz C， Wunsch A， Bödeker C， et al. Effect of pressure and gas type on intraabdominal， subcutaneous， and blood pH inlaparoscopy[J]. Surg Endosc， 2000， 14(4)：367-371.
  21. 21. Yavuz Y， Rønning K， Lyng O， et al. Effect of carbon dioxide pneumoperitoneum on tissue blood flow in the peritoneum， rectus abdominis， and diaphragm muscles[J]. Surg Endosc， 2003， 17(10)：1632-1635.
  22. 22. Wildbrett P， Oh A， Naundorf D， et al. Impact of laparoscopic gases on peritoneal microenvironment and essential parameters of cell function[J]. Surg Endosc， 2003， 17(1)：78-82.
  23. 23. Schlotterbeck H， Greib N， Dow WA， et al. Changes in coretemperature during peritoneal insufflation：comparison of two CO2 humidification devices in pigs[J]. J Surg Res， 2011， 171(2)：427-432.
  24. 24. Neuhaus SJ， Watson DI. Pneumoperitoneum and peritonealsurface changes：a review[J]. Surg Endosc， 2004， 18(9)：1316-1322.
  25. 25. Whelan RL， Franklin M， Holubar SD， et al. Postoperative cell mediated immune response is better preserved after laparoscopic vs. open colorectal resection in humans[J]. Surg Endosc， 2003， 17(6)：972-978.
  26. 26. Gitzelmann CA， Mendoza-Sagaon M， Talamini MA， et al.Cell-mediated immune response is better preserved by laparoscopy than laparotomy[J]. Surgery， 2000， 127(1)：65-71.
  27. 27. Wichmann MW， Hüttl TP， Winter H， et al. Immunologicaleffects of laparoscopic vs. open colorectal surgery：a prospective clinical study[J]. Arch Surg， 2005， 140(7)：692-697.
  28. 28. Brokelman WJ， Lensvelt M， Borel Rinkes IH， et al. Peritoneal changes due to laparoscopic surgery[J]. Surg Endosc， 2011， 25(1)：1-9.
  29. 29. Waiwut P， Shin MS， Inujima A， et al. Gomisin N enhances TNF-α-induced apoptosis via inhibition of the NF-κB and EGFR survival pathways[J]. Mol Cell Biochem， 2011， 350(1-2)：169-175.
  30. 30. Amin AT， Shiraishi N， Ninomiya S， et al. Increased mRNA expression of epidermal growth factor receptor， human epidermal receptor， and survivin in human gastric cancer after the surgical stress of laparotomy versus carbon dioxide pneumoperitoneum in a murine model[J]. Surg Endosc， 2010， 24(6)：1427-1433.
  31. 31. Tawfik Amin A， Shiraishi N， Ninomiya S， et al. Activation of nuclear factor kappa B and induction of migration inhibitory factor in tumors by surgical stress of laparotomy versus carbon dioxide pneumoperitoneum：an animal experiment[J]. Surg Endosc， 2010， 24(3)：578-583.
  32. 32. Machado MC， Coelho AM， Martins JO， et al. CO2 abdominal insufflation decreases local and systemic inflammatory response in experimental acute pancreatitis[J]. Pancreas， 2010， 39(2)：175-181.
  33. 33. Yu Y， Kuebler J， Groos S， et al. Carbon dioxide modifies the morphology and function of mesothelial cells and facilitates transepithelial neuroblastoma cell migration[J]. Pediatr Surg Int， 2010， 26(1)：29-36.
  34. 34. Fuganti PE， Rodrigues Júnior AJ， Rodrigues CJ， et al. Acomparison of the effects of pneumoperitoneum and laparotomy on natural killer cell mediated cytotoxicity and Walker tumor growth in Wistar rats[J]. Surg Endosc， 2006， 20(12)：1858-1861.
  35. 35. Mutsaers SE， Whitaker D， Papadimitriou JM. Changes in the concentration of microvilli on the free surface of healing mesothelium are associated with alterations in surface membrane charge[J]. J Pathol， 1996， 180(3)：333-339.
  36. 36. Ryan GB， Grobéty J， Majno G. Mesothelial injury and recovery[J]. Am J Pathol， 1973， 71(1)：93-112.
  37. 37. Rosário MT， Ribeiro U Jr， Corbett CE， et al. Does CO2 pneumoperitoneum alter the ultra-structuture of the mesothelium?[J]. J Surg Res， 2006， 133(2)：84-88.
  38. 38. Du J， Yu PW， Tang B. Application of stereology to study the effects of pneumoperitoneum on peritoneum[J]. Surg Endosc， 2011， 25(2)：619-627.
  39. 39. Yamaguchi K， Hirabayashi Y， Suematsu T， et al. Hyaluronic acid secretion during carbon dioxide pneumoperitoneum and its association with port-site metastasis in a murine model[J]. Surg Endosc， 2001， 15(1)：59-62.
  40. 40. Volz J， Köster S， Schaeff B， et al. Laparoscopic surgery：the effects of insufflation gas on tumor-induced lethality in nude mice[J]. Am J Obstet Gynecol， 1998， 178(4)：793-795.
  41. 41. Metzelder M， Kuebler J， Shimotakahara A， et al. CO2 pneumoperitoneum increases systemic but not local tumor spread after intraperitoneal murine neuroblastoma spillage in mice[J]. Surg Endosc， 2008， 22(12)：2648-2653.
  42. 42. Nestler G， Schulz HU， Tautenhahn J， et al. Effects of theangiogenesis inhibitor angiostatin on the growth of CC531 colon carcinoma cells in vitro and in a laparoscopic animal model of peritoneal carcinomatosis[J]. Int J Colorectal Dis， 2006， 21(4)：314-320.
  43. 43. 孫鐵為， 李強(qiáng)， 王鋒. 一次性CO2氣腹環(huán)境下氟尿嘧啶對(duì)大鼠腫瘤細(xì)胞生長(zhǎng)及轉(zhuǎn)移的影響[J]. 中國(guó)普外基礎(chǔ)與臨床雜志， 2009， 16(7)：545-549.
  44. 44. Nakada H， Ishida H， Hashimoto D， et al. Influence of different pneumoperitoneal pressures on tumor cell distribution in rats[J]. Surg Endosc， 2005， 19(4)：563-568.
  45. 45. Volz J， Volz-Köster S， Kanis S， et al. Modulation of tumor-induced lethality after pneumoperitoneum in a mouse model[J]. Cancer， 2000， 89(2)：262-266.
  46. 46. Fondrinier E， Descamps P， Arnaud JP， et al. Carbon dioxidepneumoperitoneum and peritoneal carcinosis：review[J].J Gynecol Obstet Biol Reprod (Paris)， 2002， 31(1)：11-27.