Tumor seeding during colonoscopy linked to metachronous colorectal cancer

By Marilynn Larkin

NEW YORK (Reuters Health) - 28/8/2019

Tumor seeding may occur during colonoscopy, although the risk is low, a proof-of-principle study reveals.

Three percent of patients who have undergone surgery for colorectal cancer (CRC), have recurrence of (metachronous) CRC," according to Dr. L. M. G. Moons of University Medical Center in Utrecht, the Netherlands and colleagues.

To determine whether tumor seeding could increase the risk, the authors studied data on 22 patients from the Dutch National Pathology Registry with a diagnosis of CRC from 2013 - 2015, and a second CRC diagnosis between six months and 3.5 years after surgery. Pathology reports were reviewed to identify likely metachronous CRC - i.e., histologically proven adenocarcinoma located elsewhere in the colon or rectum from the surgical anastomosis.

"We ascribed the most likely etiology to tumor seeding when endoscopic manipulations, such as biopsies or polypectomy, occurred at the location where the metachronous tumor was subsequently detected, after endoscopic manipulation of the primary tumor," the authors stated.

The team also collected clinical data from patients and compared molecular profiles of the primary and metachronous colorectal tumors using next-generation sequencing. They tested whether tumor cells stay behind in the working channel of the endoscope after biopsies of colorectal tumors and whether the cells maintained viability in organoid cultures.

As reported online August 13 in Gastroenterology, tumor seeding was suspected as the most likely etiology of metachronous CRC in five patients (ages 48 to 66; three males).

Tumor tissues were available from three of them, and in each case, an identical molecular signature was observed in the primary and metachronous colorectal tumors.

By contrast, in five control cases with a different etiology of metachronous CRC, the molecular signatures of the primary and metachronous tumor were different.

To quantify the risk of tumor seeding, the team reviewed 2,147 patient records, estimating the number of patients at risk for tumor seeding (denominator) and the number of patients in which tumor seeding had likely occurred (numerator).

Among the 310 at risk for mechanical tumor seeding, two additional cases were identified. The team concluded that, overall, the risk of tumor seeding during colonoscopy was 0.3% - 0.6%.

Further analyses demonstrated that the working channel of the colonoscope became contaminated with viable tumor cells during biopsy collection, and that subsequent instruments introduced through this working channel also became contaminated. In addition, the tumor cells were shown to have maintained their proliferative potential.

Dr. Mark Pochapin, Director of the Division of Gastroenterology and Hepatology at NYU Langone Health in New York City, commented by email, "The article provides very compelling evidence to suggest that after the discovery of a malignant-appearing colonic mass on colonoscopy, the practice of taking biopsies for histologic diagnosis should be done as the last part of the procedure."

"If biopsies of a malignant-appearing mass are done first, it is possible that 'tumor seeding' can occur from residual tumor cells left behind in the working channel of the scope," he told Reuters Health. "If a benign polyp is discovered after the scope channel is contaminated with tumor cells, these tumor cells could get picked up by the instruments used for polyp removal and seed the normal tissue, allowing for a metachronous cancer to develop at that site."

"Prior to this study," he said, "I had always been concerned about the theoretical risk of tumor seeding and avoided doing any further intervention during a colonoscopy after taking biopsies of malignant-appearing tissue."

"This study confirms the concern of tumor seeding and should alter the order in which we approach findings during a colonoscopy when a malignant tumor is suspected," he said. "Recognizing the risk of tumor seeding, all polyps should be removed BEFORE biopsies are taken of a malignant- appearing mass."

Dr. Niket Sonpal a professor at Touro College of Osteopathic Medicine in Harlem, New York City, disagreed with the study findings.

"Though this one study shows a potential issue, it is still just one study with some serious confounds," he told Reuters Health by email. "What we know of colon cancer is that mutations in genes along with environmental factors play a role. Therefore, the fact that a second lesion was found to be genetically similar to the first could simply just be that person's genetics, and...not because of a previous biopsy."

"It is interesting to think about, but the clinical implications are dire," he said. "Colorectal screening has shown great benefit in preventing CRC and studies such as this would would cause unnecessary concern for the population."

"I would assume that our inherent steps in tissue sampling and using new biopsy forceps alone would be enough (to prevent tumor seeding)," he said. "The chances, even by the authors' own accord, seem low - and many times, things that pan out in vitro do not in vivo."

Dr. Moons did not provide a comment.

SOURCE: http://bit.ly/2U93mCo

Gastroenterol 2019.

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