Laboratory of Richard L. Whelan, MD
Principal Investigator
Richard L. Whelan, MD
Background for Research focus:
Surgical trauma has been shown to stimulate establishment and growth of tumor cells. Specifically, tumor cell proliferation rates have been shown to increase and apoptosis to decrease after laparotomy in murine models. In an experimental study that assessed the ability of pre- and postoperative murine plasma to support tumor cell growth in vitro, significantly greater growth was noted in cultures to which post laparotomy plasma (from postoperative days 2 and 4) had been added. In a human study carried out by our laboratory, similar in vitro results were noted when preoperative and postoperative day 1 plasma from humans that underwent major open abdominal surgery was similarly assessed. It was postulated that a surgery-related plasma factor accounted for the differences observed. Using Western Blot analysis and ELISA it was demonstrated that major open surgery was associated with a notable decrease in the concentration of a natural cell growth regulatory protein, IGFBP-3.
Main Focus of the Laboratory:
The laboratory is studying the effect of surgical trauma on natural tumor resistance as well as on agents that might mitigate the impact of surgery related stress. The latter includes both the conventional and minimally invasive techniques. The laboratory is investigating surgery induced alterations in immuno-inflammatory axis, soluble cell growth factors and their binding proteins, as well as proteases that affect integrity of these factors. In the future, the entire list of surgery induced alterations will be uncovered using the DNA microarray technology. The purpose of these studies is to improve natural tumor resistance in the postoperative period via minimally invasive surgery or by using bioactive agents. Therapeutic agents that are able to improve immune response or to directly suppress tumor growth are being studied. Currently, we are conducting a clinical trial on the effect of GM-CSF in colon cancer patients that undergo open or minimally invasive surgery.
Current Projects:
- The effect of post-surgical IGFBP-3 depletion on colon cancer recurrence
- Matalloproteinases and their induced IGFBP-3 depletion following open and laparosopic surgery
- The effect of open and laparoscopic surgery on T cell gene expression in humans and experimental animals
- Carcinogenesis in IGFBP-3 transgenic mice
- The impact of warmed and humidified CO2 for laparoscopic bowel resection on serum IL-6 levels postoperatively.
- Randomized Phase 1 type trial examining the safety of intrabdominal irrigation with a dilute betadine solution.
- Randomized, multicenter trial comparing laparoscopic-assisted and hand-assisted methods for left and total abdominal colectomy (with Applied Medical Company, projected start date, Fall ’04.
- Prospective study examining the efficacy of the EPDU Magnetic Locating Device (Olympus Corporation) during colonoscopy both as a training tool and in the hands of experienced endoscopists.
Recent Publications
Kirman I, Poltaratskaia N, Cekic V, Forde KA, Ansari P, Boulay C, Whelan RL. Depletion of circulating insulin-like growth factor binding protein 3 after open surgery is associated with high interleukin-6 levels. Dis Colon Rectum 2004 PMID: 15085435.
Kirman I, Huang EH, Whelan RL B cell response to tumor antigens is associated with depletion of B progenitors in murine colocarcinoma. Surgery. 2004;135:313-8.
Kirman I, Jenkins D, Fowler R, Whelan RL. Naturally occurring antibodies to epithelial cell adhesion molecule (EpCAM). Dig Dis Sci 2003;48:2306-9.
Lee SW, Feingold DL, Carter JJ, Zhai C, Stapleton G, Gleason N, Whelan RL. Peritoneal macrophage and blood monocyte functions after open and laparoscopic-assisted cecectomy in rats. Surg Endosc 2003;17:1996-2002. PMID: 14569448.
Carter JJ, Feingold DL, Kirman I, Oh A, Wildbrett P, Asi Z, Fowler R, Huang E, Whelan RL. Laparoscopic-assisted cecectomy is associated with decreased formation of postoperative pulmonary metastases compared with open cecectomy in a murine model. Surgery 2003;134:432-
Kirman I, Poltoratskaia N, Herlyn D, Whelan RL. Addition of interleukin-12 to GA733 tumor protein vaccine leads to development of tumor protective immunity despite surgical stress. Surg Endosc 2003. PMID: 12658425.
Kirman I, Cekic V, Poltaratskaia N, Asi Z, Conte S, Feingold D, Forde KA, Huang EH, Whelan RL. The percentage of CD31+ T cells decreases after open but not laparoscopic surgery. Surg Endosc. 2003;17:754-7.
Whelan RL. Open versus laparoscopy assisted colectomy. Lancet 2003;361:75.
Kirman I, Maydelman A, Asi Z, Whelan RL. Effect of surgical trauma on epithelial cell adhesion molecule (GA-733) vaccine-induced tumor resistance. Surg Endosc 2003;17:505-9.
Kirman I, Cekic V, Poltaratskaia N, Asi Z, Bessler M, Huang EH, Forde KA, Whelan RL. Plasma from patients undergoing major open surgery stimulates in vitro tumor growth: Lower insulin-like growth factor binding protein 3 levels may, in part, account for this change. Surgery 2002;132:186-92.
Recent (last 5 years) Surgery Residents:
Joseph J. Carter, postdoctoral clinical fellow. E-mail jc2369@columbia.edu
Catherine A. Boulay, resident. E-mail : cad32@columbia.edu
Parswa Ansari, resident. E-mail pa63@columbia.edu
Patricia Sylla , resident. E-mail ps609@columbia.edu
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