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Colorectal cancer risk increased with bariatric surgery

Major finding: The risk of colorectal cancer increased by 60% among obese patients, a mean of 7 years after bariatric surgery but was only slightly increased among obese patients who did not undergo surgery, over the expected rate.

Data source: A retrospective cohort study using national patient registry data in Sweden compared the risk of colorectal cancer in about 15,000 obese patients who had undergone bariatric surgery and among about 62,000 obese patients who did not have surgery, compared to matched controls.

Disclosures: The study was supported by the Swedish Research Council. The authors had no conflicts of interest to declare.

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More study needed to resolve results

It is well established that overweight and obese individuals have a higher incidence of certain types of cancer; such as breast, colorectal, and endometrial to name a few. The exact mechanism is not known but it is generally linked with chronic inflammation associated with adipocyte release of inflammatory cytokines, an increase in sex steroid hormones, and an increase in insulin resistance. Therefore, it would seem logical to suggest that with significant and sustained weight loss (with or without bariatric surgery) the risk of cancer development may be reduced. Unfortunately, the data on weight loss and subsequent reduction in cancer risk are not solid. This is in part attributed to the fact that significant and sustained weight loss is extremely difficult to achieve without bariatric surgery.

There are several reports that show a protective effect of bariatric surgery on future cancer risk. Christou and colleagues (Surg. Obese Relat. Dis. 2008;4:691-5) reported that obese adults who undergo bariatric surgery may reduce their risk of developing some cancers by as much as 80%. Adams and colleagues (Obesity 2009;17:796-802) compared 6,596 patients who had gastric bypass with 9,442 severely obese individuals who had not, and found a significant decrease in the incidence of cancer and cancer-related deaths after bariatric surgery.

This report by Derogar and colleagues, published in Annals of Surgery, is the first to suggest that bariatric surgery is associated with an increased risk of colorectal cancer over time. It is difficult to interpret the results, however, as they directly contradict other reports and our general understanding of obesity and cancer. There are clearly limitations with the retrospective design of the study and the omission of any body weight or weight loss data. In addition, certain colorectal cancer risk factors, such as family history of cancer and prior adenomatous polyps, are not controlled for between the two groups.

Furthermore, there is a notion that individuals who undergo bariatric surgery tend to be more proactive about their health and take actions to prevent cancer. The authors suggest a possible mechanism that may be related to an increase in putative mucosal biomarkers of colorectal cancer risk and mucosal proinflammatory gene expression following Roux-en-Y gastric bypass. Also, a high-protein diet can promote detrimental metabolic profiles promoting carcinogenesis in the colon and rectum.

The exact mechanism remains elusive and as in most biologic systems, the answer in the end will be complex. Further research is needed to help answer some of these questions. This paper is important because it again highlights the increased risk of cancer associated with obesity and it is important for bariatric surgery programs to implement the proper screening protocols for cancer detection and prevention. Patients who undergo bariatric surgery should be screened both pre- and postoperatively as currently recommended depending on whether they are at average or high risk for certain cancers, such as breast or colon cancer, where screening has been shown to be effective.

Dr. Alex Nagle, FACS, is director of bariatric surgery, Northwestern Memorial Hospital, and associate professor of surgery, Northwestern University Feinberg School of Medicine, Chicago. He disclosed no conflicts of interest.


 

FROM THE ANNALS OF SURGERY

The risk of colorectal cancer was significantly increased among people who had undergone obesity surgery in a retrospective cohort study of more than 77,000 obese patients enrolled in a Swedish registry.

The increased risk for colorectal cancer was associated with all three bariatric procedures – vertical banded gastroplasty, adjustable gastric banding, and Roux-en-Y gastric bypass – and increased further over time, reported Dr. Maryam Derogar, of the Karolinska Institutet, Stockholm, and her associates. No such pattern over time was seen among the obese patients who did not have surgery.

"Our data suggest that increased colorectal cancer risk may be a long-term consequence of such surgery," they concluded. If the association is confirmed, they added, "it should stimulate research addressing colonoscopic evaluation of the incidence of colorectal adenomatous polyps after obesity surgery with a view to defining an optimum colonoscopy surveillance strategy for the increasing number of patients who undergo obesity surgery. The study was published online in the Annals of Surgery (2013 [doi:10.1097/SLA.0b013e318288463a]).

To address their "unexpected" finding in an earlier study of an apparent increase in the risk of colorectal cancer after obesity surgery, but no increase in the risk of other cancers related to obesity, they conducted a retrospective cohort study using national registry data between 1980 and 2009, of 15,095 obese patients who had undergone obesity surgery and 62,016 patients who had been diagnosed with obesity but did not undergo surgery. They calculated the colorectal cancer risk using the standardized incidence ratio (SIR), the observed number of cases divided by the number of expected cases in that group.

Over a median of 10 years, there were 70 colorectal cancers in the obesity surgery group; and over a median of 7 years, 373 among those who had no surgery. The SIR for colorectal cancer among those who had surgery was 1.60, which was statistically significant. Among those who had no surgery, there was a small, insignificant increase in risk group (a SIR of 1.26). In the surgery group, the risk increased over time in men and women, up to a twofold increased risk among those patients followed for at least 10 years, a pattern than was not observed in the obese patients who had no surgery.

The "substantial increase in colorectal cancer risk, above that associated with excess body weight alone, more than 10 years after surgery is compatible with the long natural history of colorectal carcinogenesis from normal mucosa to a malignant colorectal cancer," the authors wrote. Why the risk was increased is not clear, but one possible explanation could be that the malabsorption effects of the gastric bypass procedure results in local mucosal changes, the authors speculated. Previously, they had identified rectal mucosal hyperproliferation in patients who had undergone obesity surgery, present at least 3 years after the procedure, a finding that was "associated with increased mucosal expression of the protumorigenic cytokine macrophage migration inhibitory factor," they wrote.

The study’s strengths included the size of the sample, long follow-up, and the validity of Swedish national registry data, while the limitations included the retrospective design and the lack of data on body weight over time.

As in the United States and other countries, obesity has been increasing in Sweden, with a corresponding increase in bariatric surgery. Over the last 20 years, the prevalence of obesity in Sweden has doubled, and the annual number of obesity operations performed has increased from 1,500 in 2006 to almost 4,000 in 2009, according to the authors.

The study was supported by the Swedish Research Council. The authors had no conflicts of interest to declare.

emechcatie@frontlinemedcom.com

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