A Tumor Suppressor Protein Remains at Higher Levels After Laporascopic Surgery Compared With Traditional Open Surgery

Sep 4, 2002

The traditional "open" operation for colorectal cancer, done via a single lengthy incision, may lead to more cancer recurrences than operations carried out using minimally invasive methods, also known as laparoscopic methods, according to new molecular evidence from a clinical study by Columbia researchers.

Led by Dr. Richard L. Whelan, associate professor of surgery at Columbia University College of Physicians & Surgeons and site director of the Minimal Access Surgery Center at NewYork-Presbyterian Hospital's Columbia University Medical Center, the study demonstrated that plasma from patients who had undergone major open surgery was depleted of a protein that inhibits tumor growth and is normally present in the blood. The findings will be published in the August peer-reviewed journal Surgery.

The tumor suppressor protein in question is called insulin-like growth factor binding protein 3 (IGF-BP3). Preoperative IGF-BP3 levels were similar in patients who underwent open and laparoscopic procedures, but the laparoscopic operations did not appreciably lower the level of this protective, tumor suppressor protein.

In the study, plasma samples from 84 patients who underwent a colon operation for cancer or a gastric bypass for obesity were collected prior to and after surgery; 45 of the operations were open and 39 laparoscopic. The majority of operations were for colon cancer. Plasma samples were added to test tubes containing cultured tumor cells; 48 hours later the number of tumor cells in each test tube was determined.

The researchers found that the open patient's plasma taken 1 day after the operation stimulated the tumor cells to grow to a significantly greater extent than did their pre-operative (pre-op) plasma. The degree of tumor growth stimulation correlated directly with the length of the incision. No differences in tumor growth were noted when the laparoscopic group's pre- and post-operative plasma was similarly assessed.

The results of other experiments suggested that decreased levels of IGF-BP3 was the cause of the increased tumor growth observed with the open post-op plasma. The addition of IGF-BP3 to the open patient's post-op plasma lowered the tumor cell growth rate to the level observed with the pre-op plasma samples. Further, the addition of antibodies to IGF-BP3 to preop plasma increased the tumor stimulatory effect of the plasma.

Unfortunately, in a significant proportion of colorectal cancer patients, viable tumor cells are in the bloodstream even after the tumor has been surgically removed. Dr. Whelan says laparoscopic patients with higher levels of IGF-BP3 may be better able to prevent the tumor cells which remain after surgery from successfully forming tumor metastases.

Whether the replacement or administration of IGF-BP3 impacts long-term survival is unknown. Dr. Whelan and his collaborators are performing animal studies to determine if replacement of the lost IGF-BP3 immediately after surgery decreases the rate of tumor recurrences and cancer-related mortality. Additional clinical studies of patients undergoing cancer resection will help define the length of time the plasma protein alterations persist.

The findings of the Columbia study are significant, Dr. Whelan says, in light of the results of a randomized prospective trial of patients with colorectal cancer carried out in Barcelona, Spain, which were published in the June 2002 issue of The Lancet. The Spanish trial, headed by Dr. Antonio Lacy of the University of Barcelona, assessed the long-term survival and tumor recurrence of 208 colorectal cancer patients randomly assigned to undergo either an open or a laparoscopic large bowel resection. Dr. Lacy found that the cancer-related survival of the laparoscopic group was significantly higher than the survival rate of the open patient group. Significantly fewer tumor recurrences also occurred in the minimally invasive surgery group compared with the open group. At the time the data were gathered for the Lancet report, the average follow-up for the patients was 43 months.

"The Spanish trial suggests that the open method of removing the colon is associated with a worse long-term outcome," Dr. Whelan says. "Our study suggests a possible mechanism that might account, at least in part, for the survival and recurrence differences noted by Lacy and his colleagues."

"These studies have far-reaching implications," Dr. Whelan says. "The use of laparoscopic methods for the curative resection of large bowel malignancies, as well as other tumors, remains controversial although these studies suggest the minimally invasive procedure may be more beneficial."

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