DOI QR코드

DOI QR Code

Experimental Study on Sustained-release 5-Fluorouracil Implantation in Canine Peritoneum and Para-aortic Abdominalis

  • Wei, Guo (Department of General Surgery, Changhai Hospital Affiliated to The Second Military Medical University) ;
  • Nie, Ming-Ming (Department of General Surgery, Changhai Hospital Affiliated to The Second Military Medical University) ;
  • Shen, Xiao-Jun (Department of General Surgery, Changhai Hospital Affiliated to The Second Military Medical University) ;
  • Xue, Xu-Chao (Department of General Surgery, Changhai Hospital Affiliated to The Second Military Medical University) ;
  • Ma, Li-Ye (Department of General Surgery, Changhai Hospital Affiliated to The Second Military Medical University) ;
  • Du, Cheng-Hui (Department of General Surgery, Changhai Hospital Affiliated to The Second Military Medical University) ;
  • Wang, Shi-Liang (Controlled-Release Drug Laboratory, Hefei University of Technology) ;
  • Bi, Jian-Wei (Controlled-Release Drug Laboratory, Hefei University of Technology)
  • Published : 2014.01.15

Abstract

Objective: To observe local and systemic toxicity after sustained-release 5-fluorouracil (5-Fu) implantation in canine peritoneum and para-aortic abdominalis and the changes of drug concentration in the local implanted tissue with time. Methods: 300 mg sustained-release 5-Fu was implanted into canine peritoneum and para-aorta abdominalis. Samples were taken 3, 5, 7 and 10 days after implantation for assessment of changes and systemic reactions. High performance liquid chromatography was applied to detect the drug concentrations of peritoneal tissue at different distances from the implanted site, lymphatic tissue of para-aortic abdominalis, peripheral blood and portal venous blood. Results: 10 days after implantation, the drug concentrations in the peritoneum, lymphatic tissue and portal vein remained relatively high within 5 cm of the implanted site. There appeared inflammatory reaction in the local implanted tissue, but no visible pathological changes such as cell degeneration and necrosis, and systemic reaction like anorexia, nausea, vomiting and fever. Conclusions: Sustained-release 5-Fu implantation in canine peritoneum and para-aortic abdominalis can maintain a relatively high tumour-inhibiting concentration for a longer time in the local implanted area and portal vein, and has mild local and systemic reactions. Besides, it is safe and effective to prevent or treat recurrence of gastrointestinal tumours and liver metastasis.

Keywords

References

  1. Alexander HR Jr, Bartlett DL, Pingpank JF, et al (2013). Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma. Surgery, 153, 779-86. https://doi.org/10.1016/j.surg.2013.01.001
  2. Chen WP, He X, Ye QF, et al (2006). Implantation of a drug delivery system during surgery for patients with primary hepatocarcinoma. Hepatobiliary Pancreat Dis Int, 5, 391-5.
  3. Davis JL, Pandalai P, Ripley RT, et al (2011). Regional chemotherapy in locally advanced pancreatic cancer: RECLAP trial. Trials, 12, 129. https://doi.org/10.1186/1745-6215-12-129
  4. Halhsscy MT, Dunn JA, Ward LC, et al (1994). The second British stomach cancer group trial of adjuvant radiotherapy or chemotherapy in rescetable gastric cancer: five year follow-up. Lancet, 343, 1309-12. https://doi.org/10.1016/S0140-6736(94)92464-3
  5. Hu XF, Yao J, Gao SG, et al (2013). Nrf2 overexpression predicts prognosis and 5-fu resistance in gastric cancer. Asian Pac J Cancer Prev, 14, 5231-5. https://doi.org/10.7314/APJCP.2013.14.9.5231
  6. Huang B, Sun Z, Wang Z, et al (2013). Factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer: a retrospective study of a prospectively-collected database. BMC Cancer, 4, 13-57.
  7. Jarnagin WR, Schwartz LH, Gultekin DH, et al (2009). Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trialand assessment of DCE-MRI as a biomarker of survival. Ann Oncol, 20, 1589-95. https://doi.org/10.1093/annonc/mdp029
  8. Kirchhoff T, Zender L, Merkesdal S, et al (2005). Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver. World J Gastroenterol, 11, 1091-5. https://doi.org/10.3748/wjg.v11.i8.1091
  9. Link KH, Gansauge F, Gorich J, et al (1997). Palliative and adjuvant regional chemotherapy in pancreatic cancer. Eur J Surg Oncol, 23, 409-14. https://doi.org/10.1016/S0748-7983(97)93720-3
  10. Muchmore JH, Preslan JE, George WJ (1996). Regional chemotherapy for inoperable pancreatic carcinoma. Cancer, 78, 664-73. https://doi.org/10.1002/(SICI)1097-0142(19960801)78:3<664::AID-CNCR47>3.0.CO;2-U
  11. Nordlinger B, Rougier P, Arnaud JP, et al (2005). Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II-III colorectal cancer: a multicentre randomised controlled phase III trial. Lancet Oncol, 6, 459-68. https://doi.org/10.1016/S1470-2045(05)70222-9
  12. Orii T, Karasawa Y, Kitahara H, et al (2013). Long-term survival after sequential chemotherapy and surgery for advanced gastric cancer. Int J Surg Case Rep, 4, 976-80. https://doi.org/10.1016/j.ijscr.2013.07.031
  13. Oshima T, Shan J, Okugawa T, et al (2013). Down-regulation of claudin-18 is associated with the proliferative and invasive potential of gastric cancer at the invasive front. PLoS One, 8, e74757. https://doi.org/10.1371/journal.pone.0074757
  14. Pohlen U, Rieger H, Kunick-Pohlen S, et al (2007). Phase II study of regional chemotherapy using the hypoxic abdominal perfusion technique in advanced abdominal carcinoma. 5-FU pharmacokinetics, complications and outcome. Anticancer Res, 27, 667-74.
  15. Wan NB, Zhang L, Zuo CH, et al (2012). Clinical application of intrapertoneal hyperthermo-chemotherapy combined with sustained-release fluorouracil implantation in progressive gastric cancer during surgery. J Chin Phys, 14, 763-6.
  16. Wang R, Wang ZC, Liu XY, et al (2012). An experimental study on local and systemic reactions after sustained-release fluorouracil implantation. Shandong Med J, 14, 763-6.
  17. Wang X, Song ZF, Xie RM, et al (2013). Analysis of death causes of in-patients with malignant tumors in Sichuan Cancer Hospital of China from 2002 to 2012. Asian Pac J Cancer Prev, 14, 4399-402. https://doi.org/10.7314/APJCP.2013.14.7.4399
  18. Wei GL, Huang XE, Huo JG, et al (2013). Phase II study on pemetrexed-based chemotherapy in treating patients with metastatic gastric cancer not responding to prior palliative chemotherapy. Asian Pac J Cancer Prev, 14, 2703-6. https://doi.org/10.7314/APJCP.2013.14.5.2703
  19. Yamamoto M, Baba H, Kakeji Y, et al (2004). Prognostic significance of tumor markers in peritoneal lavage in advanced gastric cancer. Oncology, 67, 19-26. https://doi.org/10.1159/000080281
  20. Yao Z, Guo H, Yuan Y, et al (2013). Retrospective analysis of docetaxel, oxaliplatin plus fluorouracil compared with epirubicin, cisplatin and fluorouracil as firstline therapy for advanced gastric cancer. J Chemother, 9, 341-9.
  21. Yoney A, Isikli L (2013). Can capecitabine be used instead of concurrent bolus 5-FU in postoperative chemoradiotherapy for gastric adenocarcinoma? Asian Pac J Cancer Prev, 14, 5127-31. https://doi.org/10.7314/APJCP.2013.14.9.5127
  22. Yoshimura F, Inaba K, Kawamura Y, et al (2011). Clinical outcome and clinicopathological characteristics of recurrence after laparoscopic gastrectomy for advanced gastric cancer. Digestion, 83, 184-90. https://doi.org/10.1159/000322032
  23. Zare A, Mahmoodi M, Mohammad K, et al (2013). Survival analysis of patients with gastric cancer undergoing surgery at the Iran cancer institute: a method based on multi-state models. Asian Pac J Cancer Prev, 14, 6369-73. https://doi.org/10.7314/APJCP.2013.14.11.6369
  24. Zhang M, Li Z, Zhao B, et al (2011). Predictors of longterm survival in large gastric carcinoma patients. Hepatogastroenterology, 58, 2162-5.
  25. Zhang M, Zhang H, Ma Y, et al. Prognosis and surgical treatment of gastric cancer invading adjacent organs. ANZ J Surg, 80, 510-4.
  26. Zhang X, Zhu H, Wu X, et al (2013). A genetic polymorphism in TOX3 is associated with survival of gastric cancer in a Chinese population. PLoS One, 8, e72186. https://doi.org/10.1371/journal.pone.0072186
  27. Zhou J, Zhou ZP, Cheng S, et al (2008). Clinical research on hypotonic intrapertoneal hyperthermo-chemotherapy combined with fibrin glue sustained-release fluorouracil implantation in progressive gastric cancer during surgery. Chin Arch Gen Surg, 4, 35-7.

Cited by

  1. Phase II Study on EANI Combined with Hydrochloride Palonosetron for Prevention of Chemotherapy-induced Nausea and Vomiting Following Highly Emetogenic Chemotherapy vol.15, pp.9, 2014, https://doi.org/10.7314/APJCP.2014.15.9.3951