Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Surgery Today
Published in: Surgery Today 10/2014

01-10-2014 | Original Article

The impact of surgical extent and sex on the hepatic metastasis of colon cancer

Authors: Liat Sorski, Ben Levi, Lee Shaashua, Elad Neeman, Marganit Benish, Pini Matzner, Aviad Hoffman, Shamgar Ben-Eliyahu

Published in: Surgery Today | Issue 10/2014

Login to get access

Abstract

Purpose

Extensive oncological surgeries were previously suggested to increase cancer recurrence rates. We herein studied the impact of different surgical procedures and sex on colorectal cancer liver metastasis, employing several tumor inoculation approaches in BALB/c mice.

Methods

Experimental hepatic metastases of the syngeneic CT26 colorectal cancer line were induced either by intra-portal inoculation or intra-splenic inoculation, employing different tumor loads. Following intra-splenic inoculation, the entire spleen or an injected hemi-spleen was removed. Additionally, the magnitude of the surgical trauma accompanying the injection procedure was manipulated.

Results

Increasing the surgical trauma by adding laparotomy or extending the length of the surgery and hypothermia did not significantly affect the number of liver metastases or liver weight for any of the injection methods and tumor loads. The development of metastasis was significantly greater in males than in females under all conditions studied—a difference not explained by the direct effects of sex hormones on in vitro CT26 proliferation or vitality.

Conclusion

Concurring with less controlled clinical observations, the surgical extensiveness did not significantly affect CT26 hepatic metastasis, potentially due to a ceiling effect of the surgical trauma on the metastatic process. The sexual dimorphism observed for the CT26 metastasis should be investigated in the context of surgical stress and considering anti-CT26 immunoreactivity.
Literature
1.
2.
O’Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst. 2004;96:1420–5.PubMedCrossRef
3.
Akiyoshi T, Kobunai T, Watanabe T. Recent approaches to identifying biomarkers for high-risk stage II colon cancer. Surg Today. 2012;42:1037–45.PubMedCrossRef
4.
Morris EJ, Forman D, Thomas JD, Quirke P, Taylor EF, Fairley L, et al. Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg. 2010;97:1110–8.PubMedCrossRef
5.
Jamison RL, Donohue JH, Nagorney DM, Rosen CB, Harmsen WS, Ilstrup DM. Hepatic resection for metastatic colorectal cancer results in cure for some patients. Arch Surg. 1997;132:505–10 discussion 511.PubMedCrossRef
6.
Heslin MJ, Medina-Franco H, Parker M, Vickers SM, Aldrete J, Urist MM. Colorectal hepatic metastases: resection, local ablation, and hepatic artery infusion pump are associated with prolonged survival. Arch Surg. 2001;136:318–23.PubMedCrossRef
7.
Tan EK, Ooi LL. Colorectal cancer liver metastases—understanding the differences in the management of synchronous and metachronous disease. Ann Acad Med Singap. 2010;39:719–33.PubMed
8.
Mayo SC, Pawlik TM. Current management of colorectal hepatic metastasis. Expert Rev Gastroenterol Hepatol. 2009;3:131–44.PubMedCrossRef
9.
Ben-Eliyahu S. The promotion of tumor metastasis by surgery and stress: immunological basis and implications for psychoneuroimmunology. Brain Behav Immun. 2003;17(Suppl 1):S27–36.PubMedCrossRef
10.
Shakhar G, Ben-Eliyahu S. Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients? Ann Surg Oncol. 2003;10:972–92.PubMedCrossRef
11.
Benish M, Ben-Eliyahu S. Surgery as a double-edged sword: a clinically feasible approach to overcome the metastasis-promoting effects of surgery by blunting stress and prostaglandin responses. Cancers. 2010;2:1929–51.PubMedCrossRefPubMedCentral
12.
Tan KY, Konishi F. Long-term results of laparoscopic colorectal cancer resection: current knowledge and what remains unclear. Surg Today. 2010;40:97–101.PubMedCrossRef
13.
Kuhry E, Schwenk WF, Gaupset R, Romild U, Bonjer HJ: Long-term results of laparoscopic colorectal cancer resection. Cochrane Database Syst Rev 2008:CD003432.
14.
Glasner A, Avraham R, Rosenne E, Benish M, Zmora O, Shemer S, et al. Improving survival rates in two models of spontaneous postoperative metastasis in mice by combined administration of a beta-adrenergic antagonist and a cyclooxygenase-2 inhibitor. J Immunol. 2010;184:2449–57.PubMedCrossRef
15.
Lee JW, Shahzad MM, Lin YG, Armaiz-Pena G, Mangala LS, Han HD, et al. Surgical stress promotes tumor growth in ovarian carcinoma. Clin Cancer Res. 2009;15:2695–702.PubMedCrossRefPubMedCentral
16.
Isbert C, Boerner A, Ritz JP, Schuppan D, Buhr HJ, Germer CT. In situ ablation of experimental liver metastases delays and reduces residual intrahepatic tumour growth and peritoneal tumour spread compared with hepatic resection. Br J Surg. 2002;89:1252–9.PubMedCrossRef
17.
Kollmar O, Schilling MK, Menger MD. Experimental liver metastasis: standards for local cell implantation to study isolated tumor growth in mice. Clin Exp Metastasis. 2004;21:453–60.PubMedCrossRef
18.
Thalheimer A, Otto C, Bueter M, Illert B, Gattenlohner S, Gasser M, et al. Tumor cell dissemination in a human colon cancer animal model: orthotopic implantation or intraportal injection? Eur Surg Res. 2009;42:195–200.PubMedCrossRef
19.
Kim IY, Yan X, Tohme S, Ahmed A, Cordon-Cardo C, Shantha Kumara HM, et al. CpG ODN, Toll like receptor (TLR)-9 agonist, inhibits metastatic colon adenocarcinoma in a murine hepatic tumor model. J Surg Res. 2012;174(2):284–90.PubMedCrossRef
20.
Chiodoni C, Stoppacciaro A, Sangaletti S, Gri G, Cappetti B, Koezuka Y, et al. Different requirements for alpha-galactosylceramide and recombinant IL-12 antitumor activity in the treatment of C-26 colon carcinoma hepatic metastases. Eur J Immunol. 2001;31:3101–10.PubMedCrossRef
21.
Giavazzi R, Jessup JM, Campbell DE, Walker SM, Fidler IJ. Experimental nude mouse model of human colorectal cancer liver metastases. J Natl Cancer Inst. 1986;77:1303–8.PubMed
22.
Lafreniere R, Rosenberg SA. A novel approach to the generation and identification of experimental hepatic metastases in a murine model. J Natl Cancer Inst. 1986;76:309–22.PubMed
23.
Kasuya H, Kuruppu DK, Donahue JM, Choi EW, Kawasaki H, Tanabe KK. Mouse models of subcutaneous spleen reservoir for multiple portal venous injections to treat liver malignancies. Cancer Res. 2005;65:3823–7.PubMedCrossRef
24.
Jain A, Slansky JE, Matey LC, Allen HE, Pardoll DM, Schulick RD. Synergistic effect of a granulocyte-macrophage colony-stimulating factor-transduced tumor vaccine and systemic interleukin-2 in the treatment of murine colorectal cancer hepatic metastases. Ann Surg Oncol. 2003;10:810–20.PubMedCrossRef
25.
Levi B, Benish M, Goldfarb Y, Sorski L, Melamed R, Rosenne E, et al. Continuous stress disrupts immunostimulatory effects of IL-12. Brain Behav Immun. 2011;25:727–35.PubMedCrossRefPubMedCentral
26.
Page GG, Fennelly AM, Littleton-Kearney MT, Ben-Eliyahu S. Male–female differences in the impact of beta-adrenoceptor stimulation on resistance to experimental metastasis: exploring the effects of age and gonadal hormone involvement. J Neuroimmunol. 2008;193:113–9.PubMedCrossRefPubMedCentral
27.
Yovel G, Shakhar K, Ben-Eliyahu S. The effects of sex, menstrual cycle, and oral contraceptives on the number and activity of natural killer cells. Gynecol Oncol. 2001;81:254–62.PubMedCrossRef
28.
Naor R, Domankevich V, Shemer S, Sominsky L, Rosenne E, Levi B, et al. Metastatic-promoting effects of LPS: sexual dimorphism and mediation by catecholamines and prostaglandins. Brain Behav Immun. 2009;23:611–21.PubMedCrossRefPubMedCentral
29.
Corbett TH, Griswold DP Jr, Roberts BJ, Peckham JC, Schabel FM Jr. Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. Cancer Res. 1975;35:2434–9.PubMed
30.
Schmid I, Krall WJ, Uittenbogaart CH, Braun J, Giorgi JV. Dead cell discrimination with 7-amino-actinomycin D in combination with dual color immunofluorescence in single laser flow cytometry. Cytometry. 1992;13:204–8.PubMedCrossRef
31.
Shiromizu A, Suematsu T, Yamaguchi K, Shiraishi N, Adachi Y, Kitano S. Effect of laparotomy and laparoscopy on the establishment of lung metastasis in a murine model. Surgery. 2000;128:799–805.PubMedCrossRef
32.
Pera M, Nelson H, Rajkumar SV, Young-Fadok TM, Burgart LJ. Influence of postoperative acute-phase response on angiogenesis and tumor growth: open vs. laparoscopic-assisted surgery in mice. J Gastrointest Surg. 2003;7:783–90.PubMedCrossRef
33.
Whelan RL, Franklin M, Holubar SD, Donahue J, Fowler R, Munger C, et al. Postoperative cell mediated immune response is better preserved after laparoscopic vs open colorectal resection in humans. Surg Endosc. 2003;17:972–8.PubMedCrossRef
34.
Schwenk W, Haase O, Neudecker J, Muller JM. Short term benefits for laparoscopic colorectal resection. Cochrane Database Syst Rev. 2005:CD003145.
35.
Kaiser AM, Kang JC, Chan LS, Vukasin P, Beart RW Jr. Laparoscopic-assisted vs. open colectomy for colon cancer: a prospective randomized trial. J Laparoendosc Adv Surg Tech A. 2004;14:329–34.PubMedCrossRef
36.
Liang JT, Huang KC, Lai HS, Lee PH, Jeng YM. Oncologic results of laparoscopic versus conventional open surgery for stage II or III left-sided colon cancers: a randomized controlled trial. Ann Surg Oncol. 2007;14:109–17.PubMedCrossRef
37.
Friedrich M, Rixecker D, Friedrich G. Evaluation of stress-related hormones after surgery. Clin Exp Obstet Gynecol. 1999;26:71–5.PubMed
38.
Marana E, Scambia G, Maussier ML, Parpaglioni R, Ferrandina G, Meo F, et al. Neuroendocrine stress response in patients undergoing benign ovarian cyst surgery by laparoscopy, minilaparotomy, and laparotomy. J Am Assoc Gynecol Laparosc. 2003;10:159–65.PubMedCrossRef
39.
Muzii L, Marana R, Marana E, Paielli FV, Meo F, Maussier ML, et al. Evaluation of stress-related hormones after surgery by laparoscopy or laparotomy. J Am Assoc Gynecol Laparosc. 1996;3:229–34.PubMedCrossRef
40.
Wichmann MW, Huttl TP, Winter H, Spelsberg F, Angele MK, Heiss MM, et al. Immunological effects of laparoscopic vs open colorectal surgery: a prospective clinical study. Arch Surg. 2005;140:692–7.PubMedCrossRef
41.
Ishizu K, Sunose N, Yamazaki K, Tsuruo T, Sadahiro S, Makuuchi H, et al. Development and characterization of a model of liver metastasis using human colon cancer HCT-116 cells. Biol Pharm Bull. 2007;30:1779–83.PubMedCrossRef
42.
de Jong GM, Aarts F, Hendriks T, Boerman OC, Bleichrodt RP. Animal models for liver metastases of colorectal cancer: research review of preclinical studies in rodents. J Surg Res. 2009;154:167–76.PubMedCrossRef
43.
44.
Calle EE, Miracle-McMahill HL, Thun MJ, Heath CW Jr. Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women. J Natl Cancer Inst. 1995;87:517–23.PubMedCrossRef
45.
Newcomb PA, Zheng Y, Chia VM, Morimoto LM, Doria-Rose VP, Templeton A, et al. Estrogen plus progestin use, microsatellite instability, and the risk of colorectal cancer in women. Cancer Res. 2007;67:7534–9.PubMedCrossRef
46.
Slattery ML, Anderson K, Samowitz W, Edwards SL, Curtin K, Caan B, et al. Hormone replacement therapy and improved survival among postmenopausal women diagnosed with colon cancer (USA). Cancer Causes Control. 1999;10:467–73.PubMedCrossRef
47.
Smirnoff P, Liel Y, Gnainsky J, Shany S, Schwartz B. The protective effect of estrogen against chemically induced murine colon carcinogenesis is associated with decreased CpG island methylation and increased mRNA and protein expression of the colonic vitamin D receptor. Oncol Res. 1999;11:255–64.PubMed
48.
Xu X, Thomas ML. Estrogen receptor-mediated direct stimulation of colon cancer cell growth in vitro. Mol Cell Endocrinol. 1994;105:197–201.PubMedCrossRef
49.
Di Domenico M, Castoria G, Bilancio A, Migliaccio A, Auricchio F. Estradiol activation of human colon carcinoma-derived Caco-2 cell growth. Cancer Res. 1996;56:4516–21.PubMed
50.
Arai N, Strom A, Rafter JJ, Gustafsson JA. Estrogen receptor beta mRNA in colon cancer cells: growth effects of estrogen and genistein. Biochem Biophys Res Commun. 2000;270:425–31.PubMedCrossRef
51.
Nakayama Y, Sakamoto H, Satoh K, Yamamoto T. Tamoxifen and gonadal steroids inhibit colon cancer growth in association with inhibition of thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system. Cancer Lett. 2000;161:63–71.PubMedCrossRef
52.
Fiorelli G, Picariello L, Martineti V, Tonelli F, Brandi ML. Functional estrogen receptor beta in colon cancer cells. Biochem Biophys Res Commun. 1999;261:521–7.PubMedCrossRef
53.
Motylewska E, Lawnicka H, Melen-Mucha G. Oestradiol and tamoxifen inhibit murine Colon 38 cancer growth and increase the cytotoxic effect of fluorouracil. Endokrynol Pol. 2007;58:426–34.PubMed
54.
Hartman J, Edvardsson K, Lindberg K, Zhao C, Williams C, Strom A, et al. Tumor repressive functions of estrogen receptor beta in SW480 colon cancer cells. Cancer Res. 2009;69:6100–6.PubMedCrossRef
55.
Saydjari R, Townsend CM Jr, Barranco SC, Thompson JC. Cyclosporine and alpha-difluoromethylornithine exhibit differential effects on colon and pancreatic cancer in vitro. Invest New Drugs. 1987;5:251–8.PubMed
56.
Ben-Eliyahu S, Rosenne E, Sorski L, Levi B. Second thoughts on the role of glucocorticoids in the in vivo suppression of NK activity following stress [abstract]. In: Seventeenth annual meeting of the PsychoNeuroImmunology Reaserch society, 2010 June 2–5, Dublin, Ireland. Abstract in a meeting program.
Metadata
Title
The impact of surgical extent and sex on the hepatic metastasis of colon cancer
Authors
Liat Sorski
Ben Levi
Lee Shaashua
Elad Neeman
Marganit Benish
Pini Matzner
Aviad Hoffman
Shamgar Ben-Eliyahu
Publication date
01-10-2014
Publisher
Springer Japan
Published in
Surgery Today / Issue 10/2014
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-013-0768-1

Other articles of this Issue 10/2014

Surgery Today 10/2014 Go to the issue

Original Article

Therapeutic experience with primary liposarcoma from the sigmoid mesocolon accompanied with well-differentiated liposarcomas in the pelvis

Original Article

Functional and pathological characteristics of reversible remodeling in a canine right ventricle in response to volume overloading and volume unloading

Original Article

Zero frequency of internal hernias after laparoscopic double loop gastric bypass without closure of mesenteric defects

Original Article

Factors affecting survival after resection of intrahepatic cholangiocarcinoma

Review Article

Surgical techniques for implanting implantable cardioverter defibrillators in children and infants

Case Report

Off-pump coronary artery bypass grafting for a left main lesion due to cardiac allograft vasculopathy in Japan: first report of a case