Surgical Considerations: Margins, Adhesions, and Desmoids

GIST Support International posed questions about surgical margins and potential consequences of surgery for gastrointestinal stromal tumors (GISTs) to Raphael E. Pollock, MD PhD FACS. Dr. Pollock is the Head of the Division of Surgery at MD Anderson Cancer Center, as well as Professor & Chairman of the Department of Surgical Oncology. In addition to his medical degree, he earned a doctorate in immunology. Dr. Pollock’s practice and research are devoted entirely to soft tissue sarcoma, and he has published widely concerning sarcoma surgery and treatment. His funded research includes molecular biology of sarcomas, the role of the p53 tumor suppressor gene in soft tissue sarcoma, modulation of angiogenesis in soft tissue sarcoma, mechanisms of soft tissue sarcoma chemoresistance, as well as the development of novel therapeutics for this group of diseases.

Before answering our questions, Dr. Pollock reminded readers as follows that each patient’s situation is different. Dr. Pollock stated ”Please bear in mind that my answers to your questions represent my own personal understanding of these issues in general. Such a general understanding is never a replacement for the specific advice that a patient may receive from the surgeon who has been entrusted with the care of that patient. Moreover, the opinions that I have expressed do not represent an official opinion of the Sarcoma Center of the University of Texas MD Anderson Cancer Center.”

Surgical Margins

Although patients often refer to “clean” or “clear” surgical margins, surgeons use the term “negative” margins for the same concept.

• "R0" resection indicates complete removal of all tumor with microscopic examination of margins showing no tumor cells.
• "R1" resection indicates that the margins of the resected parts show tumor cells when viewed microscopically.
• “R2" resection indicates that portions of tumor visible to the naked eye were not removed.

1. Please explain negative margins for GIST in these two situations:

a) A wedge resection of the stomach or a segmental resection of bowel, when only a small portion of the organ where the GIST originated is removed

b) An “en bloc” resection, when portions of adjacent organs surrounding the GIST are removed together with the tumor.

“Negative Margins” is a term that surgical oncologists and pathologists employ; it means that there are no tumor cells identified at any of the edges of the resected specimen. There are times when an en bloc resection is needed to achieve negative margins, and this can mean that adjacent organs (or segments of these organs) need to be removed as part of the resection. At other times a wedge resection of an organ containing the GIST tumor may be sufficient to achieve a negative margin. The margins per se are by definition the outer most edge of the tumor resection such that if an adjacent organ or parts thereof are removed (to achieve a margin negative en bloc resection) then the margin, by definition, would be the outermost edges of the tissues removed.

2. What about all the other organs the body of the GIST was touching? If the GIST lifts away without adhering to adjacent organs, then are there any "margins" there?

That situation is called a “radial margin”, meaning that there were no additional immediately attached adjacent organs or other normal tissues attached to or being infiltrated by the tumor. The implication in that circumstance is that a better negative margin cannot be achieved by resecting additional normal tissues that might be in the immediate area of the tumor if the tumor was not growing into these normal tissues.

3. What about when a tumor must be dissected away from one of the great blood vessels? Can we assume that the microscopic margins there are NOT negative margins?

Not necessarily; sometimes it is possible to dissect in between the actual blood vessel and tissues that closely surround the blood vessel. In so doing the closely surrounding tissues may provide a margin of tissue between the edge of the tumor and the blood vessel such that the final tumor resection margin is negative.

4. Some research finds no difference in GIST recurrence for patients whose surgical margins showed microscopic evidence of tumor cells (R1 resection) than for those who had no tumor cells at the margin (R0 resection). Might this be related to the probability that the GIST had already shed cells into the abdominal cavity? Does this shedding make surgical margins less relevant?

This is a very complex and controversial question whose definitive answer will require more time and experience than we currently have available. GIST cells shed into the abdominal cavity can account for recurrence. Were it possible to prove that such shedding had already occurred then achieving negative margins might not be quite as imperative. It is also important to bear in mind that the large majority of R1 resections do not recur, whereas 7-10% of R0 resections (microscopic negative margins of resection) are noted to recur. We try to do everything possible to tip the balance in favor of the patient but we certainly do not have all of the answers.

5. Most GISTs are within the peritoneal cavity, but some GISTs of the duodenum and colon are retroperitoneal. What difference might this make in terms of the likelihood that shed cells will find a good place to grow within the abdomen or to get into the bloodstream and metastasize elsewhere?

We do not have definitive information that a retroperitoneal versus intra-abdominal site of GIST primary tumor might make a difference regarding shed cells implanting at the site of the primary tumor or spreading elsewhere in the body.

Adhesions

6. Is it understood why some people develop adhesions and others do not, or are there hypotheses about this?

Adhesions develop primarily as a means to bring additional blood to tissues that have been manipulated during surgical procedures; however, their formation does not mean that a surgeon has been less than gentle regarding intra-operative tissue handling. Repeat surgery, which may be needed if a patient develops tumor recurrence, is the single largest factor which predisposes a patient to form adhesions.

7. Can a patient do anything to minimize adhesion formation or to minimize the discomfort they cause?

I am not aware of anything that a patient can do to minimize adhesion formation; the discomfort that they cause should be treated with non-specific (and non-addicting) agents.

Desmoids or Fibromatosis

8. Can surgery sometimes trigger formation of desmoids?

This is also an area of controversy. In some patients a previous surgical experience appears to be an inciting factor, but this is exceedingly difficult to prove in a controlled fashion.

9. Some patients have both GIST and desmoids. Is this probably due to surgery, or may there be more to the association between these 2 tumor types?

There are indeed some patients who have both GIST and desmoids. This co-occurrence is probably not due to surgery. Instead, it may be due to a molecular trigger (or triggers) that may function in common in both the GIST and the desmoid that a specific patient may harbor, and is the subject of investigation in the laboratory at this time.