Skip to main content

Advertisement

Log in

Colonic stent-induced mechanical compression may suppress cancer cell proliferation in malignant large bowel obstruction

  • Published:
Surgical Endoscopy Aims and scope Submit manuscript

Abstract

Background

The short-term safety and efficacy of insertion of a self-expandable metallic colonic stent (SEMS) followed by elective surgery, “bridge to surgery (BTS)”, for malignant large bowel obstruction (MLBO) have been well described; however, the influence on long-term oncological outcomes is unclear. The aim of this study was to evaluate changes in oncological characteristics in colorectal cancer (CRC) tissues after SEMS insertion, focusing on growth factors, cell cycle and apoptosis.

Methods

From January 2013 to September 2014, a total of 25 patients with MLBO who underwent BTS at our single institution were retrospectively included. Paired CRC tissue samples before (endoscopic biopsy) and after SEMS insertion (surgically resected) were collected from each patient. EGFR, VEGF, Ki-67, p27kip1 and TUNEL expression were determined by immunohistochemistry.

Results

No clinical or subclinical perforations evaluated by mechanical ulceration pathologically were observed. Epithelial exfoliation, tumour necrosis, infiltration of inflammatory cells and fibrosis were observed in SEMS-inserted surgically-resected specimens. Overall, 84% (21/25) and 60% (15/25) of patients exhibited no change or a decrease in staining category, respectively, for EGFR and VEGF expression after SEMS insertion. A significant decrease in Ki-67 expression was observed in surgically-resected specimens compared with endoscopic biopsy specimens (P < 0.01). The upstream cell cycle inhibitor, p27kip1, was significantly increased after SEMS insertion (P = 0.049).

Conclusions

Although the long-term safety of BTS should be determined in a future clinical trial, mechanical compression by SEMS may suppress cancer cell proliferation and this result could provide some insights into the issue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Dauphine CE, Tan P, Beart RW Jr, Vukasin P, Cohen H, Corman ML (2002) Placement of self-expanding metal stents for acute malignant large-bowel obstruction: a collective review. Ann Surg Oncol 9:574–579

    Article  PubMed  Google Scholar 

  2. Deans GT, Krukowski ZH, Irwin ST (1994) Malignant obstruction of the left colon. Br J Surg 81:1270–1276

    Article  CAS  PubMed  Google Scholar 

  3. Yeo HL, Lee SW (2013) Colorectal emergencies: review and controversies in the management of large bowel obstruction. J Gastrointest Surg 17:2007–2012

    Article  PubMed  Google Scholar 

  4. Barillari P, Aurello P, De Angelis R, Valabrega S, Ramacciato G, D’Angelo F, Fegiz G (1992) Management and survival of patients affected with obstructive colorectal cancer. Int Surg 77:251–255

    CAS  PubMed  Google Scholar 

  5. Tekkis PP, Kinsman R, Thompson MR, Stamatakis JD, Association of Coloproctology of Great Britain and Ireland (2004) The Association of Coloproctology of Great Britain and Ireland study of large bowel obstruction caused by colorectal cancer. Ann Surg 240:76–81

    Article  PubMed  PubMed Central  Google Scholar 

  6. Pearce NW, Scott SD, Karran SJ (1992) Timing and method of reversal of Hartmann’s procedure. Br J Surg 79:839–841

    Article  CAS  PubMed  Google Scholar 

  7. Dohmoto M (1991) New method: endoscopic implantation of rectal stent in palliative treatment of malignant stenosis. Endosc Dig 3:1507–1512

    Google Scholar 

  8. Saida Y, Enomoto T, Takabayashi K, Otsuji A, Nakamura Y, Nagao J, Kusachi S (2011) Outcome of 141 cases of self-expandable metallic stent placements for malignant and benign colorectal strictures in a single center. Surg Endosc 25:1748–1752

    Article  PubMed  Google Scholar 

  9. Saito S, Yoshida S, Isayama H, Matsuzawa T, Kuwai T, Maetani I, Shimada M, Yamada T, Tomita M, Koizumi K, Hirata N, Kanazawa H, Enomoto T, Sekido H, Saida Y (2016) A prospective multicenter study on self-expandable metallic stents as a bridge to surgery for malignant colorectal obstruction in Japan: efficacy and safety in 312 patients. Surg Endosc 30:3976–3986

    Article  PubMed  Google Scholar 

  10. Cirocchi R, Farinella E, Trastulli S, Desiderio J, Listorti C, Boselli C, Parisi A, Noya G, Sagar J (2013) Safety and efficacy of endoscopic colonic stenting as a bridge to surgery in the management of intestinal obstruction due to left colon and rectal cancer: a systematic review and meta-analysis. Surg Oncol 22:14–21

    Article  PubMed  Google Scholar 

  11. Huang X, Lv B, Zhang S, Meng L (2014) Preoperative colonic stents versus emergency surgery for acute left-sided malignant colonic obstruction: a meta-analysis. J Gastrointest Surg 18:584–591

    Article  PubMed  Google Scholar 

  12. Tan CJ, Dasari BV, Gardiner K (2012) Systematic review and meta-analysis of randomized clinical trials of self-expanding metallic stents as a bridge to surgery versus emergency surgery for malignant left-sided large bowel obstruction. Br J Surg 99:469–476

    Article  CAS  PubMed  Google Scholar 

  13. Gorissen KJ, Tuynman JB, Fryer E, Wang L, Uberoi R, Jones OM, Cunningham C, Lindsey I (2013) Local recurrence after stenting for obstructing left-sided colonic cancer. Br J Surg 100:1805–1809

    Article  CAS  PubMed  Google Scholar 

  14. Matsuda A, Miyashita M, Matsumoto S, Matsutani T, Sakurazawa N, Takahashi G, Kishi T, Uchida E (2015) Comparison of long-term outcomes of colonic stent as “bridge to surgery” and emergency surgery for malignant large-bowel obstruction: a meta-analysis. Ann Surg Oncol 22:497–504

    Article  PubMed  Google Scholar 

  15. Sabbagh C, Browet F, Diouf M, Cosse C, Brehant O, Bartoli E, Mauvais F, Chauffert B, Dupas J, Nguyen-Khac E, Regimbeau J (2013) Is stenting as “a bridge to surgery” an oncologically safe strategy for the management of acute, left-sided, malignant, colonic obstruction? A comparative study with a propensity score analysis. Ann Surg 258:107–115

    Article  PubMed  Google Scholar 

  16. Kim SJ, Kim HW, Park SB, Kang DH, Choi CW, Song BJ, Hong JB, Kim DJ, Park BS, Son GM (2015) Colonic perforation either during or after stent insertion as a bridge to surgery for malignant colorectal obstruction increases the risk of peritoneal seeding. Surg Endosc 29:3499–3506

    Article  PubMed  Google Scholar 

  17. Sloothaak DA, van den Berg MW, Dijkgraaf MG, Fockens P, Tanis PJ, van Hooft JE, Bemelman WA, Collaborative Dutch Stent-In Study Group (2014) Oncological outcome of malignant colonic obstruction in the Dutch Stent-In 2 trial. Br J Surg 101:1751–1757

    Article  CAS  PubMed  Google Scholar 

  18. Adler DG, Young-Fadok TM, Smyrk T, Garces YI, Baron TH (2002) Preoperative chemoradiation therapy after placement of a self-expanding metal stent in a patient with an obstructing rectal cancer: clinical and pathologic findings. Gastrointest Endosc 55:435–437

    Article  PubMed  Google Scholar 

  19. Amini N, Haydel D, Reisian N, Sempa G, Chu J, Wang Q, Zhao G, Stamos MJ, Wu ML (2012) Colorectal stents orient specimens and induce artifacts that mimic Crohn disease. Int J Surg Pathol 20:161–168

    Article  PubMed  Google Scholar 

  20. Fryer E, Gorissen KJ, Wang LM, Guy R, Chetty R (2015) Spectrum of histopathological changes encountered in stented colorectal carcinomas. Histopathology 66:480–484

    Article  PubMed  Google Scholar 

  21. Kusayanagi S, Kaneko K, Yamamura F, Hirakawa M, Miyasaka N, Konishi K, Kurahashi T, Yoshikawa N, Tsunoda A, Kusano M, Mitamura K (2002) Histological findings after placement of a self-expanding stent in rectal carcinoma with complete obstruction—case report. Hepatogastroenterology 49:412–415

    CAS  PubMed  Google Scholar 

  22. Cao D, Hou M, Guan YS, Jiang M, Yang Y, Gou HF (2009) Expression of HIF-1alpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications. BMC Cancer 9:432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Takahashi N, Yamada Y, Taniguchi H, Honma Y, Iwasa S, Kato K, Hamaguchi T, Shimada Y (2014) Combined assessment of epidermal [corrected] growth factor receptor dual color in situ hybridization and immunohistochemistry with downstream gene mutations in prediction of response to the anti-EGFR therapy for patients with metastatic colorectal cancer. Arch Med Res 45:366–374

    Article  CAS  PubMed  Google Scholar 

  24. Shin IY, Sung NY, Lee YS, Kwon TS, Si Y, Lee YS, Oh ST, Lee IK (2014) The expression of multiple proteins as prognostic factors in colorectal cancer: cathepsin D, p53, COX-2, epidermal growth factor receptor, C-erbB-2, and Ki-67. Gut Liver 8:13–23

    Article  PubMed  Google Scholar 

  25. Bubendorf L, Sauter G, Moch H, Schmid HP, Gasser TC, Jordan P, Mihatsch MJ (1996) Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol 178:437–441

    Article  CAS  PubMed  Google Scholar 

  26. Chen YT, Henk MJ, Carney KJ, Wong WD, Rothenberger DA, Zheng T, Feygin M, Madoff RD (1997) Prognostic significance of tumor markers in colorectal cancer patients: DNA index, S-phase fraction, p53 expression, and Ki-67 index. J Gastrointest Surg 1:266–272 (discussion 273)

    Article  CAS  PubMed  Google Scholar 

  27. Huh JW, Lee JH, Kim HR (2010) Expression of p16, p53, and Ki-67 in colorectal adenocarcinoma: a study of 356 surgically resected cases. Hepatogastroenterology 57:734–740

    PubMed  Google Scholar 

  28. Jansen RL, Hupperets PS, Arends JW, Joosten-Achjanie SR, Volovics A, Schouten HC, Hillen HF (1998) MIB-1 labelling index is an independent prognostic marker in primary breast cancer. Br J Cancer 78:460–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mueller MM, Fusenig NE (2004) Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4:839–849

    Article  CAS  PubMed  Google Scholar 

  30. Roussos ET, Condeelis JS, Patsialou A (2011) Chemotaxis in cancer. Nat Rev Cancer 11:573–587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hirschhaeuser F, Menne H, Dittfeld C, West J, Mueller-Klieser W, Kunz-Schughart LA (2010) Multicellular tumor spheroids: an underestimated tool is catching up again. J Biotechnol 148:3–15

    Article  CAS  PubMed  Google Scholar 

  32. Delarue M, Montel F, Caen O, Elgeti J, Siaugue JM, Vignjevic D, Prost J, Joanny JF, Cappello G (2013) Mechanical control of cell flow in multicellular spheroids. Phys Rev Lett 110:138103

    Article  CAS  PubMed  Google Scholar 

  33. Montel F, Delarue M, Elgeti J, Malaquin L, Basan M, Risler T, Cabane B, Vignjevic D, Prost J, Cappello G, Joanny JF (2011) Stress clamp experiments on multicellular tumor spheroids. Phys Rev Lett 107:188102

    Article  CAS  PubMed  Google Scholar 

  34. Delarue M, Montel F, Vignjevic D, Prost J, Joanny JF, Cappello G (2014) Compressive stress inhibits proliferation in tumor spheroids through a volume limitation. Biophys J 107:1821–1828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Belletti B, Baldassarre G (2012) New light on p27(kip1) in breast cancer. Cell Cycle 11:3701–3702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bottini C, Platini F, Rinaldi M, Leutner M, Alabiso O, Garavoglia M, Tessitore L (2009) p27Kip1 is inactivated in human colorectal cancer by cytoplasmic localization associated with activation of Akt/PKB. Int J Oncol 34:69–77

    CAS  PubMed  Google Scholar 

  37. Galizia G, Lieto E, Ferraraccio F, De Vita F, Castellano P, Orditura M, Imperatore V, La Mura A, La Manna G, Pinto M, Catalano G, Pignatelli C, Ciardiello F (2006) Prognostic significance of epidermal growth factor receptor expression in colon cancer patients undergoing curative surgery. Ann Surg Oncol 13:823–835

    Article  PubMed  Google Scholar 

  38. Rego RL, Foster NR, Smyrk TC, Le M, O’Connell MJ, Sargent DJ, Windschitl H, Sinicrope FA (2010) Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status. Br J Cancer 102:165–172

    Article  CAS  PubMed  Google Scholar 

  39. Licitra L, Storkel S, Kerr KM, Van Cutsem E, Pirker R, Hirsch FR, Vermorken JB, von Heydebreck A, Esser R, Celik I, Ciardiello F (2013) Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer 49:1161–1168

    Article  CAS  PubMed  Google Scholar 

  40. Fang Y, Wang Y, Wang Y, Meng Y, Zhu J, Jin H, Li J, Zhang D, Yu Y, Wu XR, Huang C (2014) A new tumour suppression mechanism by p27Kip1: EGFR down-regulation mediated by JNK/c-Jun pathway inhibition. Biochem J 463:383–392

    Article  CAS  PubMed  Google Scholar 

  41. Wu Y, Jin M, Xu H, Shimin Z, He S, Wang L, Zhang Y (2010) Clinicopathologic significance of HIF-1α, CXCR4, and VEGF expression in colon cancer. Clin Dev Immunol. https://doi.org/10.1155/2010/537531

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG (2005) Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro Oncol 7:134–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kondo Y, Arii S, Mori A, Furutani M, Chiba T, Imamura M (2000) Enhancement of angiogenesis, tumor growth, and metastasis by transfection of vascular endothelial growth factor into LoVo human colon cancer cell line. Clin Cancer Res 6:622–630

    CAS  PubMed  Google Scholar 

  44. Japan Colonic Stent Safe Procedure Research Group (2017) Colonic stent for “bridge to surgery” prospective randomized controlled trial comparing treatment with non-stenting surgery in stage II/III obstructive colon cancer (COBRA Trial). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000029703

Download references

Acknowledgements

We thank H. Nikki March, PhD, from Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript.

Author information

Authors and Affiliations

Authors

Contributions

Study concept and design: AM and SM. Acquisition of data: AM, NS, YK, KY, KS, MY, and TH. Analysis and interpretation of data: AM, and SM. Drafting of the manuscript: AM. Study supervision: MM, and HY.

Corresponding author

Correspondence to Akihisa Matsuda.

Ethics declarations

Disclosures

Drs. Akihisa Matsuda, Masao Miyashita, Satoshi Matsumoto, Nobuyuki Sakurazawa, Youichi Kawano, Kazuya Yamahatsu, Kumiko Sekiguchi, Marina Yamada, Tsutomu Hatori, and Hiroshi Yoshida have no conflicts of interest or financial ties to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsuda, A., Miyashita, M., Matsumoto, S. et al. Colonic stent-induced mechanical compression may suppress cancer cell proliferation in malignant large bowel obstruction. Surg Endosc 33, 1290–1297 (2019). https://doi.org/10.1007/s00464-018-6411-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00464-018-6411-x

Keywords

Navigation